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Iwao Ojima
Distinguished Professor of Chemistry Director, the Institute of Chemical Biology & Drug Discovery

State University of New York at Stony Brook
Iwao Ojima was born in Yokohama, Japan in 1945. He received his B.S. (1968), M.S. (1970), and Ph.D. (1973) degrees from the University of Tokyo, Japan. He joined the Sagami Institute of Chemical Research and held a position as Senior Research Fellow until 1983. He joined the faculty at the Department of Chemistry, State University of New York at Stony Brook first as Associate Professor (1983), was promoted to Professor (1984), Leading Professor (1991), and then to Distinguished Professor (1995). He served as the Department Chairman from May 1997 through October 2003. Since early 2003 he has been the founding Director of the Institute of Chemical Biology and Drug Discovery at Stony Brook. He has a wide range of research interests in synthetic organic, organometallic and medicinal chemistry, including asymmetric synthesis, organic synthesis based on homogeneous catalysis, peptide and peptide mimetics, β-lactam chemistry, enzyme inhibitors, anticancer agents, antithrombotic agents, and medicinally relevant organofluorine compounds. He is a recipient of the E. B. Hershberg Award (for Important Discovery of Medicinally Active Substances) (2001) and the Arthur C. Cope Scholar Award (1994) from the American Chemical Society; the Chemical Society of Japan Award (for distinguished achievements) (1999) and National Young Investigator’s Award from the Chemical Society of Japan (1976). He is a Fellow of the J. S. Guggenheim Memorial Foundation (1995), the American Association for the Advancement of Science (1997), and The New York Academy of Sciences (2000). He also received the Outstanding Inventor Award from The Research Foundation of the State University of New York in 2002, and a NYSTAR Faculty Development Award in 2003 from the Governor of the State of New York. He has served as an advisory committee member for the National Institutes of Health, National Science Foundation and the U.S. Department of Energy. He has served or currently serves as Editorial Advisory Board member of Journal of Organic Chemistry, Organometallics, Journal of Molecular Catalysis, Current Topics in Medicinal Chemistry (current), Medicinal Chemistry (current), and Letters in Drug Design & Discovery (current). He has published more than 340 papers and reviews in leading journals as well as edited 5 books. He currently holds or has applications pending for more than l40 patents. SciFinder lists more than 600 publications to his credits. Since he started his career in the U.S. at Stony Brook unversty in 1983, he has given more than 400 invited lectures at universities, research institutes, and industries. Also, he has given more than 70 Plenary and Invited Lectures at international conferences and symposia.

Stony Brook Symposium on New Horizons in Organic Chemistry
September 29-30, 2005 The Charles B. Wang Center Thursday, September 29
8:00 AM – 1:00 PM Registration 9:00 AM – 11:40 AM SBU Alumni Symposium 11:45 AM- 1:00 PM Buffet Lunch for Registered Participants and Poster Setup

Opening Lecture (1:00-2:00 PM)
Greetings: Dr. Robert L. McGrath, Provost Moderator: Professor Michael G. White, Chair, Department of Chemistry Professor Ryoji Noyori (Nobel Laureate in Chemistry, 2001; President, RIKEN, Japan) “Asymmetric Hydrogenation: Science and Opportunities”

Session I: Medicinal Chemistry and Drug Discovery (2:00-5:30 PM)
Moderator: 2:00 – 2:30 2:30 – 3:00 3:00 – 3:30 Professor Frank W. Fowler Professor Gunda I. Georg (University of Kansas) “Taxol: Brain Delivery” Dr. Alain Commerçon (Sanofi-Aventis, France) “New Generation Taxoids: Discovery and Development of RPR109881” Dr. John Piwinski (Schering-Plough Research Institute, NJ)) “Utilizing SAR and SBDD to Discover Novel Antiviral Agents”

3:30 – 4:00

Coffee break, Poster Session Professor Joseph W. Lauher Dr. Ezio Bombardelli (Indena, SpA, Italy) “Colchicine and its analogues as potential anticancer drugs” Dr. Ralph J. Bernacki (Roswell Park Cancer Institute) “IDN 5390, a novel seco-taxane with anti-angiogenic activity, inhibits endothelial cell motility at sub-cytotoxic concentrations”

Moderator: 4:00 – 4:30 4:30 – 5:00

5:00 – 5:30

Professor David G. I. Kingston (Virginia Tech.) “The shape of things to come: Structural and synthetic studies of Taxol and related compounds” Short talks by poster presenters Reception, Student Activity Center Ballroom B (Registered Participants Only) Symposium Banquet, Student Activity Center Ballroom A (Registered Participants Only)

5:30 – 6:15 6:15 – 7:00 7:00 – 9:30

Friday, September 30
8:00 – 8:40 8:40 Continental Breakfast, Charles B. Wang Center Greetings: Dr. James V. Staros, Dean, College of Arts and Sciences,

Session II: Synthetic Methodology and Organic Synthesis (8:45-12:30)
Moderator: 8:45 – 9:15 9:15 – 9:45 Professor Kathlyn A. Parker Professor Eiichi Negishi (Purdue University) “ZACA Reaction: Zr-Catalyzed Asymmetric Carboalumination of Alkenes” Professor Masahiro Murakami (Kyoto University, Japan) “Torque Control by Metal-Orbital Interactions”
“Designer Acid Catalysis for Selective Organic Transformation”

9:45 – 10:15 Professor Hisashi Yamamoto (University of Chicago) 10:15-10:30 Moderator: Short Coffee Break Professor Nancy S. Goroff

10:30 – 11:00 Professor Michael P. Doyle (University of Maryland) “New Advances in Catalysis with Dirhodium(II) Compounds” 11:00 – 11:30 Professor Gary A. Molander (University of Pennsylvania) “Expanding Organoboron Chemistry with Organotrifluoroborates” 11:30 – 12:00 Professor Thomas W. Bell (University of Nevada, Reno) “Synthesis and Photochemistry in Pursuit of a Light-Driven Molecular Motor” 12:00 – 12:30 Professor Eiichi Nakamura (University of Tokyo) “Organic Synthesis: The Key Science for the Future” 12:30 – 1:30 Lunch, Poster Session

Session III: Bioorganic Chemistry and Chemical Biology (1:30-5:30 PM)
Moderator: 1:30 – 2:00 2:00 – 2:30 Professor Dale G. Drueckhammer Professor Koji Nakanishi (Columbia University) “Bioorganic studies on gingkolides” Professor Peter J. Tonge (Stony Brook University) “Mycolic Acid, Menaquinone and Mycobactin Biosynthesis: Mining the Magic Mountain for Novel Tuberculosis Chemotherapeutics” Professor Scott M. Sieburth (Temple University) “Silicon as a Central Drug Design Component”

2:30 – 3:00

3:00 – 3:30

Coffee Break, Poster Session Professor Daniel P. Raleigh Professor Nicole S. Sampson (Stony Brook University) “Multivalent and Stereoregular Polymers to Probe Fertilinβ Function in Fertilization” Professor Steven Rokita (University of Maryland) “Selective Alkylation of DNA through a Recognition-Dependent Process” Professor Cynthia J. Burrows (University of Utah) “Heterocyclic Chemistry leading to Mutagenesis via Oxidation of DNA Bases” Professor Glenn D. Prestwich (University of Utah) “Injectable synthetic extracellular matrix for tissue engineering and repair”

Moderator: 3:30 – 4:00

4:00 – 4:30 4:30 – 5:00 5:00 – 5:30


Closing Remarks: Robert C. Kerber, Associate Chair, Department of Chemistry

SBU Alumni Symposium
September 29 (9:00 – 11:40 AM), 2005
8:30 – 9:00 Coffee and Danish, Charles B. Wang Center

Greetings: Dr. Donna M. Iula, Chair of Organizing Committee, Pfizer Moderator: Dr. Seung-Yub Lee, ICB & DD 9:00 – 9:20 9:20 – 9:40 Dr. Scott D. Kuduk (Merck Research Laboratories, PA) “2,3-Diaminopyridine Bradykinin B1 Receptor Antagonists” Dr. An T. Vu (Wyeth Research, PA) “2-Phenylquinolines as Potent and Selective Estrogen Receptor beta (ERβ) Ligands”

9:40 – 10:00 Professor Thierry Brigaud (Université de Cergy-Pontoise, France) “Chiral fluorinated imines and oxazolidines: synthons for organofluorine chemistry and asymmetric synthesis” 10:00 – 10:20 Dr. Joseph Zhu (Amgen, Inc., CA) “Design and Synthesis of Conformationally Constrained TRPV1 Antagonists” 10:20 – 10:40 Dr. Matthew M. Zhao (Merck Research Laboratories, NJ) “Development of the Manufacturing Process to Emend® (Aprepitant), Winner of 2005 Presidential Green Chemistry Challenge Award” 10:40 – 11:00 Dr. Ivan Habuš (Ruđer Bošković Institute, Croatia) “Diels-Alder reactions on imines derived from 3-amino-β-lactams” 11:00 – 11:20 Dr. Masakatsu Eguchi (Institute for Chemical Genomics, WA) “Design, Synthesis, and Application of Peptide Secondary Structure Mimetics” 11:20 – 11:40 Professor Elke Schoffers (Western Michigan University) “Looking for a Ligand with a New Twist? Chiral Phenanthrolines for Organic Chemistry” 11:40 Greeting and Remarks: Professor Iwao Ojima

Asymmetric Hydrogenation: Science and Opportunities
Asymmetric catalysis is four-dimensional chemistry. High efficiency can be achieved only by using a combination of both an ideal three-dimensional structure (x, y, z) and suitable kinetics (t). Although HH bonds are readily cleaved by transition metal complexes, truly useful asymmetric hydrogenations are limited. BINAP-transition metal complexes are shaped in a manner that is beneficial for chiral recognition, and these complexes can act as hydrogenation catalysts. However, their efficiency highly depends on the metal and the auxiliary anionic or neutral ligands, and the reaction conditions. No universal catalysts exist because of the diversity of unsaturated organic compounds. The means of developing efficient asymmetric hydrogenations is discussed from a mechanistic point of view.

Professor Ryoji Noyori (President, RIKEN, Japan) Nobel Laureate in Chemistry, 2001
Ryoji Noyori was born in 1938 in Japan, was educated at Kyoto University and became an Instructor in Hitosi Nozaki's group at the same university in 1963. He was appointed Associate Professor at Nagoya University in 1968, spent a postdoctoral year at Harvard with E.J. Corey in 1969–1970 and, shortly after returning to Nagoya, was promoted to Professor in 1972. In 2003, he was appointed President of RIKEN and also University Professor at Nagoya. Noyori is a Member of the Japan Academy and the Pontifical Academy of Sciences, and a Foreign Member of the National Academy of Sciences, USA, the Russian Academy of Sciences, and the Royal Society, UK. His research has long focused on the fundamentals and applications of molecular catalysis based on organometallic chemistry, particularly asymmetric catalysis and what is now known as "green chemistry”. In 2001, he received the Wolf Prize in Chemistry and the Roger Adams Award, and also shared the Nobel Prize in Chemistry with W. S. Knowles and K. B. Sharpless.

Professor Gunda I. Georg (University of Kansas)
Gunda I. Georg is a University Distinguished Professor in the Departme nt of Medicinal Chemistry at the University of Kansas. She also is the Director of the Center for Drug Discovery and the Director of the Exper imental Therapeutics Program of the Kansas Masonic Cancer Institute. She is the PI of a statewide NIH COBRE Center for Cancer Experiment al Therapeutics. She received the Dr. rer. nat. degree in Medicinal Che mistry from the University of Marburg in Germany in 1980 and was a p ostdoc in the Department of Chemistry at the University of Ottawa, Can ada. She has over 130 publications in the area of organic medicinal che mistry with a focus on the synthesis and structure-activity studies of anti cancer natural products and male contraceptive agents. She is the co-inv entor of Aquavan®, a water-soluble anesthetic, which is in phase III cli nical trails. She has served on various scientific advisory boards, for ex ample for the NIH, the American Cancer Society, and the Institute for t he Study of Aging. She is an AAAS Fellow and has received the Sato Memorial International Award of the Pharmaceutical Society of Japan a mong other honors.

Taxol: Brain Delivery
Taxol, commonly used for the treatment of breast, ovarian, and lung cancer, is not significantly absorbed across the gastrointestinal epithelium after oral administration and does not cross the bloodbrain-barrier. A primary mechanism limiting taxol distribution into the brain is active efflux by the multi-drug resistant gene product 1 (MDR1) or P-glycoprotein (Pgp) localized on the blood side of the microcerebrovascular endothelium comprising the BBB. We hypothesized that specific modifications of the taxol molecule could reduce binding or recognition by Pgp, resulting in improved BBB permeability. Our approach is based on Seelig’s suggestion that clusters of hydrogen bond acceptors (electron donating groups), arranged in fixed spatial distances from each other, are required for recognition by Pgp binding sites. The recognition elements are formed either by two or by three electron donating groups. It was also hypothesized that the number and strength of the hydrogen bonds present in a molecule determine Pgp affinity. This implies that one could remove recognition elements from the molecule that are not necessary for biological activity and improve BBB penetration. It was further observed that certain functional groups with a negative charge do not interact with Pgp. We investigated a number of taxol analogues that were modified at the 3’-amide group, at C9, C10, and C7 to test this hypothesis. The analogues were analyzed for cytotoxicity against the MCF7 breast cancer cell line and the drug resistant breast cancer cell line NCI/ADR-RES. They were also investigated for their influence on rhodamine 123 uptake into brain microvessel endothelial cells to assess interaction with Pgp. One of the derivatives, the C10 hemisuccinate analogue of Taxol (Tx-67), was also examined in an in situ rat brain perfusion experiment (J. Med. Chem. 2005, 48, 832). Several of the taxol analogues, including Tx-67 showed reduced interaction with Pgp in the BBB.

Dr. Alain Commerçon (Sanofi-Aventis, France)
2005-present : Currently head of Natural Products Chemistry at Sanofi-Aventis 2004-2005 : Senior Director at Aventis. Head of HTMC (High Throu put Medicinal Chemistry) and Coordinator of NPCT (Nat ural Product Chemistry Team) Member of the National Commissions of ARC – French Association for Cancer Research (2000-2004). Member of the board of SFC (Société Française de Chimie) Member of the board of SCT (Société de Chimie Thérapeutique) Member of the Scientific Board of Ariana Pharmaceuticals

Sanofi-aventis New Generation Taxoids: Discovery and Development of RPR109881
Cancer is still the leading cause of death throughout the world. Although chemotherapy plays the key role for treating advanced cancer, results of currently available chemotherapy regimens are still disappointing. Recently, several new compounds, such as taxanes and camptothecines, have demonstrated promising activities. Among these compounds, the taxanes, paclitaxel and docetaxel, have the same mechanism of action and have broad antitumor activity on solid tumors (e.g. breast, ovarian, lung, prostate) . These compounds interact with polymerized tubulin to promote the formation of microtubules, to prevent their disassemble, and, thus, to block cell division at the G2-M phase. At present taxanes are key compounds in chemotherapy treatment. However recurrences are common and new agents active after taxanes failure are necessary. As part of our research program on new generation taxoids, a main objective has been the targeting of resistant / refractory tumor cells. Our efforts led to the discovery of new generation compounds. Within this set of promising molecules was RPR109881, a new modified taxane generated by a serendipitous chemical rearrangement. The initial approach leading to RPR109881 will be disclosed along with preclinical data. This compound is currently undergoing clinical trials. Phase I data led to 90 mg/m2 as the recommended dose with 1h infusion duration. Recent data from Phase II against MBC (metastatic breast cancer) showed that patients tolerability was acceptable in taxotere non-resistant and taxoid resistant strata, and was similar to that reported in Phase I studies. Neutropenia was the main hematological toxicity and diarrhea the most frequent non-hematological toxicity. Efficacy data showed nearly 20% response rate for the resistant stratum. These results support the on-going evaluation of RPR109881 versus standard therapy in a randomized Phase III study of patients with MBC.

Professor David G. I. Kingston (Virginia Tech.)
1960 B.A.(Chemistry) Cambridge University, England 1964 Ph.D. (Organic Chemistry) Cambridge University, England (Advisors: Lord Todd and D.W. Cameron) 1963-1964 Research Associate, M.I.T. Cambridge, Massachusetts 1964-1966 NATO Fellow, Cambridge University 1966-1971 Assistant Professor of Chemistry, SUNY Albany 1971-present Associate Professor - University Distinguished Professor, Virginia Polytechnic Institute and State University, Blacksburg, Virginia. 1999 Research Achievement Award, American Society of Pharmacognosy 2002 Virginia Scientist of the Year, April 2002. 1983-1998 Associate Editor of the Journal of Natural Products 2000-2004 Member of NIH Bioorganic and Natural Products Chemistry Study Section.

The shape of things to come: Structural and synthetic studies of Taxol and related compounds.
Paclitaxel (TaxolTM, 1) and its semisynthetic analog docetaxel (2) are two of the most important anticancer agents developed over the last 30 years, and Professor Ojima has made major contributions to their chemistry and biology. The compounds continue to excite interest as new activities are discovered for them and their analogs. Their primary mechanism of action is by interaction with the cellular protein tubulin, causing irreversible polymerization to microtubules. A detailed knowledge of this crucial interaction is thus of paramount importance in the design and development of highly potent analogs and also for the development of “non-taxane” tubulin polymerization agents. The lecture will review our work on discovering the tubulin-binding conformation of paclitaxel by a combination of REDOR NMR and fluorescence spectroscopic studies, and by molecular modeling combined with the results of electron crystallographic studies. This work has resulted in the design and synthesis of bridged paclitaxel analogs such as 3 that have tubulin-assembly and cytotoxic activities equal to or better than those of paclitaxel. The implications of this work for the future development of paclitaxellike compounds will be discussed, and the synthesis of the simplified analog 4 will be described.

O R1

O HO HO OAc OH OCOPh 1 2 PhCONH 1 R = Ph, R = Ac 2 R1 = Me3CO, R2 = H

Dr. Ezio Bombardelli (Indena SpA)
Dr. Bombardelli is President of the Scientific Board for Research and Development of Natural Products, Indena SpA, Milan Italy. He received his B.Sc. in Biology from the University of Pavia in 1962, and completed a 5 year postdoctoral role of Assistant Professor at the Biochemistry Institute at the University of Milan, 1962-1966. In 1962 he went on to join Inverni Della Beffa SpA, Milan, Italy, as Deputy Director of Research and Development, 1962-1985. Main duties were conducting chemical research on natural products of natural semi-synthetic origin, isolation, structure elucidation, synthesis and medicinal chemistry. From 1986 he became Scientific Director of Indena SpA before becoming President. Special research interests have been Botanical Derivatives, Anti-tumour, Antiinflammatory, Anti-microbial, Anti-viral and CNS compounds. Over 390 research papers have been published and about 120 patents. He has been an active participant to many conferences and symposia, where he has presented numerous scientific papers.

Colchicine and its analogues as potential anticancer drugs
Colchicine is an alkaloid extracted from the seeds of Colchicum autumnale, a plant native of the Caucasian area and reported since the Greek Antiquity for the treatment of joints-pain. Curiously neglected in Europe for centuries, the plant was introduced in the States by Benjamin Franklin after a trip to United Kingdom where he got relief from gout by application an extract of Colchicum. The demand of colchicine in the world is today appreciably high not only because of its use in the treatment of the gout, but also because of its importance as starting material for the manufacturing its 3O-glucosyl thio-analogue, thiocolchicoside, widely used in Europe for the treatment of spasticity and muscular contractures. Colchicine is also known as an antimitotic agent and its citotoxic properties were discovered in 1889, when the Italian scientist Pernice described the influence of such an alkaloid on tissues proliferation. Nevertheless the compound is probably the oldest citotoxic drug known still lacking of any clinical application. A colchicine analogue, known with the trademark of Colcemid®, has been in use for a fairly limited period for the treatment of Hodgkin’s lymphoma. The major limiting factors of the class of colchinoids were the appreciable toxicity and the development of resistance. Believing in the potentiality of this class we kept on re-examining many natural and semisynthetic derivatives, together their thio-analogues, focusing our attention particularly on the activity against platinum resistant, taxane resistant and MDR tumours. After an extensive SAR study we found that appreciable result in vitro were obtained by modification of ring B and derivatization of nitrogen. In particular we found that dimeric derivatives of thiocolchicine, whose IDN 5404 is the lead, were extremely active against colon tumor platinum-resistant cell lines. Furthermore it has been found that those dimers, besides their classical ability to inhibit the polymerization of tubulin, are able to interact with topoisomerase I with a mechanism different from that peculiar to camptothecin. Recently, dosage formulations of IDN 5404 with human serum albumin demonstrated a consistent reduction in toxicological effects, enhancing therefore the therapeutic index of the class and opening new possibilities in the treatment of colon cancer.

Dr. Ralph J. Bernacki (Roswell Park Cancer Institute)
Pharmacology & Therapeutics Dept. Grace Cancer Drug Center, Roswell Park Institute Buffalo, NY 14263 1972-1974 1974-1976 1976-1977 1977-1980 1981-1993 1993-2000 2000-present Cancer Research Scientist I Cancer Research Scientist II Senior Cancer Research Scientist Cancer Research Scientist IV Cancer Research Scientist V Cancer Research Scientist VI Member

IDN 5390, a novel seco-taxane with anti-angiogenic activity, inhibits endothelial cell motility at sub-cytotoxic concentrations
The protracted low-dose administration of conventional chemotherapeutic agents, including the taxanes paclitaxel and docetaxel, has been shown to inhibit tumor growth by an anti-angiogenic mechanism. However, the feasibility of these two clinical agents for protracted scheduling is limited by host toxicity and poor oral bioavailibility. IDN 5390, a novel seco-taxane derivative with demonstrated anti-tumor activity, has improved oral bioavailability and a toxicity profile suitable for daily administration, rendering it an excellent candidate for protracted dosing in vivo to achieve an anti-angiogenic effect. The aims of these studies were to evaluate the in vitro activity of IDN 5390 on endothelial cell functions relevant to angiogenesis, namely endothelial cell proliferation, motility and microcapillary formation, and to compare the efficacy of IDN 5390 to paclitaxel and docetaxel. In a modified Boyden chamber migration assay, a monolayer “wound” closure assay and a capillary tube formation assay, IDN 5390 inhibited human umbilical vein endothelial cell (HUVEC) migration and capillary formation in a dose-dependent manner at concentrations that did not compromise cell viability. In contrast, paclitaxel and docetaxel, although more potent inhibitors of endothelial cell proliferation, did not exhibit selectivity for inhibition of cell migration or capillary tube formation. Further evaluation of these agents revealed that while paclitaxel, docetaxel and IDN 5390 all potently polymerized purified tubulin in vitro, IDN 5390 did not stabilize microtubules against depolymerization as potently as paclitaxel or docetaxel, suggesting that the dynamic instability of microtubules of these agents may be differentially regulated in a cellular context. Indeed, treatment of HUVEC with IDN 5390, even at high concentrations, resulted in only a transient G2/M arrest, while paclitaxel and docetaxel induced sustained G2/M arrest to an overall greater extent than IDN 5390. The in vivo anti-angiogenic activities of IDN 5390 and docetaxel were compared in a subcutaneous Matrigel plug assay of neovascularization. Docetaxel administered intravenously to mice Q3D x 3 doses at 20, 10 and 5 mg/kg/dose was compared to IDN 5390 adminstered orally, QD at 120, 60 and 30 mg/kg/dose. The antiangiogenic effect of docetaxel even at the highest dose of 20mg/kg/dose was only equal to that of IDN 5390 at the lowest dose, as determined by microvessel density in the CD31 immunnostained plug. Additionally, greater toxicity, as determined by animal weight loss, was observed among docetaxel-treated animals compared to IDN 5390-treated animals. Thus, the selective anti-motility activity on endothelial cells and the differential regulation of microtubule dynamics by IDN 5390 represent a novel mechanism of taxane drug action and a new paradigm in anti-angiogenic taxane drug development. (Supported in part by funds from Indena SpA, Milan, Italy.)

Dr. John Piwinski (Schering-Plough Research Institute, NJ)
John J. Piwinski received his B.S. degree in Chemistry and Biochemistry from the State University of New York at Stony Brook in 1976. As an undergraduate, he received his first exposure to research by working under the direction of Professor Frank W. Fowler. In 1980 he received his Ph.D. in Organic Chemistry from Yale University working with Professor Frederick E. Ziegler. He joined Revlon Health Care (USV Laboratories) in 1980 as a Senior Scientist working in the cardiovascular diseases area. In 1983 he moved to Schering-Plough where he worked in the respiratory diseases group. He was promoted to Director of Chemistry for Allergy and Immunology in 1992, to Vice President of Chemical Research in 1999 and most recently Group Vice President of Chemical Research in 2004. He also has approximately 120 published research papers, abstracts and approved U.S. patents. He is a member of the Scientific Advisory Board for the New Jersey Academy of Sciences since 1996, a member of the American Chemical Society since 1975 and most recently serves as a member for the Institute of Chemical Biology & Drug Discovery Advisory Board at SUNY at Stony Brook.

Utilizing SAR and SBDD to Discover Novel Antiviral Agents
Over the past century medicinal chemistry has played a pivotal role in the discovery of new therapeutic agents for the treatment of disease. The fundamental role of organic synthesis for investigating structure-activity relationships (SAR) to attain a desired pharmacological profile for a therapeutic agent has not changed much during this time. However, as we gained a better understanding of how therapeutic agents work at the molecular level, a new direction in the drug discovery process emerged towards the latter half of the century. Simultaneously, new methods and technologies emerged that improved the drug discovery process, such as tools to aid in structure-based drug design (SBDD). These new technologies enabled the medicinal chemist to design more potent and selective agents with improved pharmacokinetic and in vivo profiles. As a result, new medicines are being approved today that are very safe and treat diseases that previously had no cures. This presentation will illustrate how scientists have been integrating many of these new technologies to discover modern medicines. Efforts at Schering-Plough have resulted in a series of CCR5 antagonists and HCV protease inhibitors, which have resulted in compounds that are currently in clinical development for the treatment of HIV and Hepatitis C.

Professor Eiichi Negishi (Purdue University)
H. C. Brown Distinguished Professor of Chemistry, Purdue University, grew up in Japan and received his Bachelor’s degree from the University of Tokyo (1958). He then joined a chemical company, Teijin. In 1960 he came to the University of Pennsylvania on a Fulbright Scholarship and obtained his Ph.D. degree in 1963. He returned to Teijin but joined Professor H. C. Brown’s Laboratories at Purdue as a Postdoctoral Associate in 1966. He was appointed Assistant to Professor Brown in 1968. It was during the following few years that he began to see the need for some catalytic ways of promoting organoborane reactions. Negishi went to Syracuse University as Assistant Professor in 1972 and was promoted to Associate Professor in 1976. In 1979 he was invited back to Purdue University as Full Professor. In 1999 he was appointed the inaugural H. C. Brown Distinguished Professor of Chemistry. Various awards he has received include the Guggenheim Fellowship (1987), the 1996 A. R. Day Award, a 1997 Chemical Society of Japan Award, the 1998 ACS Organometallic Chemistry Award, a Humboldt Senior Researcher Award, Germany (1998 – 2001), and the 2000 RSC Sir E. Frankland Prize Lectureship. At Purdue University, he was the recipient of the 1998 McCoy Award and the 2003 Sigma Xi Award.

ZACA Reaction: Zr-Catalyzed Asymmetric Carboalumination of Alkenes
The Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) was discovered a decade ago. (i) R3Al, cat. (-)-(NMI)2ZrCl2 R
(ii) O2



R = Me, 70-80% ee R = Et or higher alkyl, 90-95% ee

The ZACA reaction represents a prototypical example of enantioselective carbon-carbon bond-forming reactions of alkenes of one-point binding. It is catalytic in both Zr and a chiral auxiliary, e.g., NMI. The enantioface selectivity of methylalumination has only been 70-80% ee, although that of ethyl- and higher alkylmetalation has been 90-95% ee. Despite the less than satisfactory enantioselectivity for methylalumination, a highly efficient asymmetric method for the synthesis of a wide range of stereochemically pure chiral organic compounds including (i) deoxypolypropionates, and (ii) reduced terpenoids, such as vitamins E and K, has been developed. The current status of the ZACA-based asymmetric method will be discussed with emphasis on several methodological breakthroughs. Some of the noteworthy transformations are shown below. In cases where the products cannot be readily purified by simple means, such as chromatography and recrystallization, the lipase-catalyzed selective acetylation may be used to produce stereoisomerically pure compounds in 60-80% recovery.
(i) Et3Al, IBAO (ii) cat. (-)-(NMI)2ZrCl2 H 3 O+




90% ee

Me3Al cat. (-)-(NMI)2ZrCl2


(i) Zn(OTf)2, DMF (ii) vinyl bromide, cat. PdLn 71% overall


75% ee


(i) Me3Al cat. (+)-(NMI)2ZrCl2 (ii) I2, (iii) TBSCl, base



(i) BuLi then ZnBr2 (ii) vinyl bromide, cat. PdLn


"One-pot" (-)-ZACA-Pd-cat. vinyl.

"One-pot" (+)-ZACA-Pd-cat. vinyl.


Professor Masahiro Murakami (Kyoto University, Japan)
1984 Doctor of Science The University of Tokyo (Prof. Mukaiyama) 1984 – 1987 Assistant, The University of Tokyo 1987 – 1993 Assistant, Kyoto University 1991 – 1992 Postdoctoral Fellow, ETH Zürich, Switzerland (Prof. Eschenmoser) 1993 – 2001 Associate Professor, Kyoto University 2002 – Present Professor, Kyoto University

Contrasteric Torque Control by Metal-Orbital Interactions
The electrocyclic ring-opening of cyclobutenes is a classical textbook example of concerted pericyclic reactions that proceed under the control of the Woodward–Hoffmann rules. Substituents located at the 3- and 4-positions can move either inward or outward during the thermal ring opening reaction. Rondan and Houk proved that the selectivity of the rotational direction, termed torquoselectivity, is subject to electronic control. We discovered the interesting preference of silyl groups to rotate inward, contradicting intuitive expectation for outward rotation based on steric grounds. The antibonding  * orbital of a silicon–carbon linkage is energetically low-lying and able to accept electron density from the HOMO of the opening cyclobutene skeleton, stabilizing the inward transition state.
H PhMe2Si H H 110   C C C Si C C H PhMe2Si H H + PhMe2Si H H 77 : 23 H

The following reaction of trans-3,4-bis(trimethylsilyl)cyclobutene presents a striking exam¬ple of contrasteric behaviors.1 In addition, exclusive inward rotation was experimentally identified with 3borylcyclo-butene.2
H Me3Si H (pin)B SiMe3 110   C H H H 92   C H H + Me3Si SiMe3 E,E-isomer

78 : 22 H (pin)B H H

1. Murakami M., Hasegawa, M. Angew. Chem. Int. Ed. 2004, 43, 4874. 2. Murakami M., Usui I., Hasegawa M., Matsuda T. J. Am. Chem. Soc. 2005, 127, 1366.

(pin)B = pinacolatoboryl


Professor Hisashi Yamamoto (University of Chicago)
Hisashi Yamamoto received his Bachelor from Kyoto University and Ph. D. from Harvard under the mentorship of Professor E. J. Corey. His first academic position was as Assistant Professor and lecturer at Kyoto University, and in 1977 he was appointed Associate Professor of Chemistry at the University of Hawaii. In 1980 he moved to Nagoya University where he became Professor in 1983. In 2002, he moved to United States as Professor at the University of Chicago. He has been honored to receive the Prelog Medal in 1993, the Chemical Society of Japan Award in 1995, the Max-Tishler Prize in 1998, Le Grand Prix de la Fondation Maison de la Chimie in 2002, National Prize of Purple Medal (Japan) in 2002, and Yamada Prize in 2004. His current interests are mainly development of new synthetic reactions in the filed of acid catalysis including designer Lewis acids, designer Brønsted acids, and combination of these two acid systems. Recently he is also interested in a new field on Niroso aldol reactions.

Designer Acid Catalysis for Selective Organic Transformation
Lewis and Brønsted acids can be utilized as more effective tools for chemical reactions by sophisticated engineering as “designer acids”. Needless to say, the ultimate goal of such “designer acids” is to achieve high reactivity, selectivity, and versatility as a useful tool o f organic synthesis. The full potential of acid catalysts has not yet been realized. One possible way to take advantage of such abilities may be to apply a “combined acids system” to the catalyst design. The concept of combined acids, which can be classified into Brønsted acid assisted Lewis acid (BLA), Lewis acid assisted Lewis acid (LLA), Lewis acid assisted Brønsted acid (LBA), and Brønsted acid assisted Brønsted acid (BBA), can be a particularly useful tool for the design of asymmetric catalysis, because combining such acids will bring out their inherent reactivity by associative interaction, and also provide more organized structure, which will allow an effective asymmetric environment to be secured.(1) Table 1 summarizes the representative examples for each acid catalysts. The other way to generate highly reactive acid catalysis is designing super Lewis acid catalysis based on super Brønsted acid systems. Several new Brønsted acids are introduced and used for selective organic transformations. The lecture will include these new trends of acid catalysis in organic synthesis.
1. H. Yamamoto and K. Futatsugi, Angew. Chem. Int. Ed. Engl., 2005, 44, 1924-1942; See also the following general introduction of acid catalysis: a) Lewis Acids in Organic Synthesis, Vols. 1 and 2 (Ed. H. Yamamoto), Wiley-VCH, Weinhelm, 2000; b) Lewis Acid Reagents: A Practical Approach (Ed. H. Yamamoto), Oxford University Press, Oxford, 1999.

Professor Michael P. Doyle (University of Maryland)
Michael P. Doyle received his B.S. degree from the College of St. Thomas in St. Paul, MN, and his Ph.D. degree from Iowa State University. Following a postdoctoral engagement , he joined the faculty at Hope College in 1968. In 1984, he moved to Trinity University in San Antonio, TX, as the Dr. D. R. Semmes Distinguished Professor of Chemistry, and in 1997 he came to Tucson, AZ, as Vice President, then President, of Research Corporation and Professor of Chemistry at the University of Arizona. In 2003 he moved to the University of Maryland, College Park, where he is Professor and Chair of the Department of Chemistry and Biochemistry. Among the awards that he has received are a Camille and Henry Dreyfus Teacher-Scholar Award (1973), a Chemical Manufacturers Association Catalyst Award (1982), the American Chemical Society Award for Research at Undergraduate Institutions (1988), Doctor Honoris Causa from the Russian Academy of Sciences (1994), Alexander von Humboldt Senior Scientist Award (1995), the James Flack Norris Award for Excellence in Undergraduate Education (1995), the George C. Pimentel Award for Chemical Education (2002), and the Arthur C. Cope Scholar Award (2006). He has written or coauthored ten books, including Basic Organic Stereochemistry, 20 book chapters, and he is the co-author of more than 250 journal publications.

New Advances in Catalysis with Dirhodium(II) Compounds
The challenge of development of catalysts that are effective for a broad range of transformations has been met with dirhodium carboxamidates. With high turnover numbers and selectivities, they are highly effective for catalytic reactions with diazo esters, as Lewis acids in catalytic processes, and as oxidation catalysts. Chiral catalysts for metal carbene transformations have been developed. Dirhodium(II) carboxamidate catalysts that possess four chiral pyrrolidone, oxazolidinone, azetidinone, or imidazolidinone ligands with pendent ester substituents are highly effective. Optical yields of greater than 95% have been achieved in intramolecular cyclopropanation reactions in alkyne cyclopropenation reactions, in gamma-lactone production from carbon-hydrogen insertion reactions of diazoacetate esters. New applications of these catalysts as Lewis acids (hetero-Diels-Alder and ketene cycloaddition reactions) and for chemical oxidations will be presented.

Professor Gary A. Molander (University of Pennsylvania)
Consultant, Hauser Chemical Research, 1991-1999. NIH Medicinal Chemistry Study Section, 1993-1997. Associate Chair, Department of Chemistry and Biochemistry, University of Colorado, 1992-1995. Elected Member-at-Large, ACS Division of Organic Chemistry Executive Committee, 1999. Executive Director, 37th National Organic Symposium, 1999-2001. Editorial Advisory Board, Organometallics, 2000-2003. Chair-Elect, Philadelphia Organic Chemists’ Club, 2000. Chair, Philadelphia Organic Chemists’ Club, 2001. Alternate Councilor, Philadelphia Section of the American Chemical Society, 2001-2003. Associate Editor, Organic Letters, 2002-. Editorial Advisory Board, Current Topics in Medicinal Chemistry, 2002-. Associate Editor, Comprehensive Organic Functional Group Transformations II, Pergamon Press, 2003-2004. Board of Consulting Editors, Tetrahedron and Tetrahedron Letters, 2003-2008. Director, Philadelphia Section of the American Chemical Society, 2004-2006. Volume Editor, Science of Synthesis, Thieme Publishers, 2004-2005. Editor, Encyclopedia of Reagents for Organic Synthesis, Wiley, 2004present. Secretary/Treasurer, ACS Division of Organic Chemistry, 2005present. Vice Chair, Department of Chemistry, University of Pennsylvania, 2005- presnet.

Expanding Organoboron Chemistry with Organotrifluoroborates
Organotrifluoroborates have emerged as complementary boron reagents for Suzuki-Miyaura type crosscoupling reactions. For many years, boronic acids, boronate esters or organoboranes have been employed as the principle organoboron partners in these transformations. However, these reagents possess many limitations. Boronic acids are notorious for the difficulty involved in their purification as well as their uncertain stoichiometry. Even though the use of boronate esters is more attractive from this point of view, these reagents lack atom economy and are more expensive to employ. Organoboranes are limited by the inherent characteristics of the in situ hydroboration reaction used to create them. These latter reagents also suffer from high sensitivity to air and poor functional group compatibility in some cases. In contrast, organotrifluoroborates are unique compounds that have been shown to overcome these limitations. These reagents can be easily prepared from inexpensive materials. They are stable to air and moisture, allowing storage for long periods of time without noticeable degradation. In fact, their high versatility and stability has made them excellent partners in SuzukiMiyaura type coupling reactions. The presentation will outline the utility and versatility of organotrifluoroborates in cross-coupling reactions. Additionally, the ability of these reagents to resist chemical oxidation will be highlighted. This feature of organotrifluoroborates offers the unique opportunity to preserve the carbon-boron bond in the oxidation of remote functionality within the same molecule.

Professor Thomas W. Bell (University of Nevada, Rino)
Thomas Bell, born in 1951, received his PhD from University College, London in 1980, having conducted his thesis research with F. Sondheimar and D.J. Cram (UCLA). He worked with J. Meinwald as an NIH Postdoctoral Fellow at Cornell University, then joined the State University of New York at Stony Brook as an Assistant Professor in 1982. There, he reached the rank of Professor in 1991, then moved to his current position as Professor of Chemistry at the University of Nevada, Reno, in 1995. He has been a Fellow of the American Association of the Advancement of Science since 1994; in 1990 and 1996 he was appointed Visiting Professor at Université Louis Pasteur in Strasbourg, France. His current interests include advanced materials, antiviral and immunomodulatory drugs, nanoscale molecular assemblies and devices, and supramolecular chemistry, as well as hiking, mountain biking, skiing and snowboarding.

Synthesis and Photochemistry in Pursuit of a Light-Driven Molecular Motor
A multidisciplinary team at UNR has planned the synthesis of a light-driven molecular motor of potential use in nanotechnology. Design and modeling of a molecular motor based on “sterically geared” 9-(2,2,2-triphenylethylidene)fluorene (1)[1] are discussed. Several substituted analogs of 1, such as the 2-tert-butyl derivative (2), have been synthesized to investigate photoisomerization efficiency. This first photoisomerization study of a dibenzofulvene reveals significant quantum yields (4 9%), despite theoretical prediction of inefficient or negligible isomerization of the parent hydrocarbon, fulvene. Polar substituents increase absorption wavelengths and can greatly enhance photoisomerization quantum yields. The current status of our efforts to synthesize the target molecular motor is also described.






[1] T.W. Bell, V. J. Catalano, M.G.B. Drew, D. J. Phillips, Chem. Eur. J., 2002, 8, 2219.

Professor Eiichi Nakamura (University of Tokyo)
Eiichi Nakamura received his first degree in chemistry with Prof. T. Mukaiyama and his Ph.D. degree in 1978 with Prof. I. Kuwajima both at Tokyo Institute of Technology. After two postdoctoral years with Prof. G. Stork at Columbia University, he started his academic career at Tokyo Institute of Technology in 1980, and in 1995, he moved to the University of Tokyo as a Professor of Physical Organic Chemistry. He is currently the Project Leader of "Nakamura Functional Carbon Cluster" ERATO Project (Japan Agency for Science and Technology) and a Senior Science Officer at the Japan Society for Promotion of Science. He is a recipient of The Japan IBM Science Prize (1993), Nagoya Medal in Organic Chemistry, Silver Meal (2001) and The Chemical Society of Japan Award (2003). He is a Fellow of the American Association for Advancement of Science and a Fellow of the Royal Society of Chemistry.

Organic Synthesis: The Key Science for the Future
Carbon clusters remain to be the subject of 2000 papers every year. While a majority of these reports are concerned with the materials per se, it is our belief that the future science of carbon clusters depends on chemically modified carbon cluster complexes and control of their nano architectures-a new challenge for synthetic chemists. Some time ago, we discovered that addition of an organocopper reagent to [60]fullerene takes place regioselectiviely to give penta-addition product.[1] The reaction is completely regioselective, often quantitative and can be carried out on a multi-gram scale with minimum synthetic skill. The adduct can be converted to a variety of metal complexes, where the fullerene cyclopentadienide (FCp) serves as a  5-ligand to the metal, an intriguing example being "bucky ferrocene".[2] We also found that metal atoms can be introduced also in a "ship-in-bottle" way into carbon nanotubes to make endohedral metallonanotubes.[3] Such engineered carbon clusters can then be transformed into one- or twodimensional nano-architectures.[4]
[1] M. Sawamura, H. Iikura, and E. Nakamura, J. Am. Chem. Soc., 118 (1996) 12850-12851. [2] A. Hashimoto, H. Yorimitsu, K. Ajima, K. Suenaga, H. Isobe, J. Miyawaki, M. Yudasaka, S. Iijima, E. Nakamura, Proc. Natl. Acad. Sci., 101 (2004) 8527-8530. [3] M. Sawamura, Y. Kuninobu, M. Toganoh, Y. Matsuo, M. Yamanaka and E. Nakamura, J. Am. Chem. Soc., 124 (2002) 9354-9355. [4] S. Zhou, C. Burger, B. Chu, M. Sawamura, N. Nagahama, M. Toganoh, U. E. Hackler, H. Isobe, and E. Nakamura, Science, 291, (2001) 1944-1947; M. Sawamura, K. Kawai, Y. Matsuo, K. Kanie, T. Kato and E. Nakamura, Nature, 419, (2002) 702-705; E. Nakamura and H. Isobe Acc. Chem. Res. 36, (2003) 807-815.

Professor Koji Nakanishi (Columbia University)
Born in Hong Kong, and brought up in Lyon, London, and Alexandria, he graduated from Nagoya University, 1947 with Fujio Egami. After 2 years of post-graduate work with Louis Fieser, Harvard University, he returned to Nagoya University where he completed his Ph.D. in 1954 with Yoshimasa Hirata He was Assistant Professor at Nagoya until 1958 and then Professor of Chemistry at Tokyo Kyoiku University. In 1963 he moved to Tohoku Univeersity, Sendai, and in 1969 joined Columbia University, becoming Centennial Professor in 1980. He was a founding member and research director of the International Centre of Insect Physiology and Ecology (ICIPE) in Kenya, 1969-1977, and 1978-1991, Director of Suntory Institute for Bioorganic Research, and was a director at Biosphere 2, Arizona, Columbia University, from April 2001, until its termination in December 2003. His research covers isolation and structural studies of natural products, vision and chiroptical spectroscopy. He discovered NMR NOE in structure determinations, determined structures of 200 natural products, published 800 papers. He has received awards from 12 countries. A Nakanishi Prize of the Am. Chem. Society and the Chem. Soc. Japan started in 1996 and is awarded in alternate years in Japan and the U.S.

Bioorganic studies on gingkolides
The tree Ginkgo biloba was mentioned in the Chinese Material Medica 5000 years. Fossil records show that the Ginbkgo genus was present 180 millionsa years ago with many widespread species. However, today only one species , G. biloba , has survived. The morphology of the Ginkgo tree appears to have changed very little for over 100 milion years and hence the name the fossil tree. The standardized extract, containing 21% flavonoids and 7% terpene trilactones (TTL), is the best selling herb selling 1 billion dollars in 1997, the main reputed activity being prevention of dementia and memory enhancement. The TTL consist of the diterpenoid ginkgolides and the sesquiterpenoid bilobalide,(1) all having tight cage structures. The TTL has attracted immense interest when it was found to be antagonists of PAFR (patelet activating factor receptor) in 1986; it has since been found that they are also ligands for several other receptors.(2,3) Despite the intense interests, their mode of action on a molecular structure level is hardly known. With such clarifications in mind, we have been performing studies on chemical conversions, preparation of photoaffinity probes and bioactivities.(4) These aspects including the finding that TTL inhibit progress of Alzheimer’s disease(5) will be presented.
(1). a) M. Maruyama, A. Terahara, Y. Nakadaira, M.C. Woods, Y. Takagi, K. Nakanishi, Tetrahedron Lett., 315 (1967). b) M.C. Woods, I. Miura, Y. Nakadaira, A. Terahara, M. Maruyama, K. Nakanishi, Tetrahedron Lett., 321 (1967). (discovery of NOE). (2). K. Stromgaard and K. Nakanishi. Angew. Chem. Int. Ed. 43, 1640 (2004) (3). S. Jaracz, K. Nakanishi,A.A.Jensen, K.Stromgaard. Chem. Eur. J, 10,150 (2004). (4). K. Nakanishi, Bioorg. Med. Chem., 13, 4987 (2005). (5). O. Vitolo, B.Gomg. Z. Cao, H. Ishii, S. Jaracz, K. Nakanishi, O. Arancio, S. Dzyuba, M. Shelanski, submitted.

Professor Peter J. Tonge (Stony Brook University)
1988-1993 1993-1994 1995-1995 1996-2000 2000-2004 1996-present 1997-present 1999-present 1999-present 1999-present 1999-present 2004-present Research Associate, Institute for Biological Sciences, NRC, Ottawa, Canada. Research Officer, Institute for Biological Sciences, NRC, Ottawa, Canada. Staff Investigator, The Picower Institute for Medical Research, Manhasset, NY Assistant Professor, Department of Chemistry, SUNY at Stony Brook. Associate Professor, Department of Chemistry, SUNY at Stony Brook. Member, Biophysics Graduate Program, Stony Brook. Member, Molecular and Cellular Biology Graduate Program, Stony Brook. Member, Biochemistry and Structural Biology Graduate Program, Stony Brook. Member, Center for Infectious Diseases, Stony Brook. Member, Molecular Genetics and Microbiology Graduate Program, Stony Brook. Member, Molecular and Cellular Pharmacology Graduate Program, Stony Brook. Member, Institute for Chemical Biology & Drug Discovery

Mycolic Acid, Menaquinone and Mycobactin Biosynthesis: Mining the Magic Mountain for Novel Tuberculosis Chemotherapeutics
Novel chemotherapeutics for treating multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread of tuberculosis, a disease that kills more than two million people annually. Using structure-based drug design we have developed a series of alkylsubstituted diphenyl ethers that are uncompetitive inhibitors of InhA, the MTB fatty acid enoyl reductase. The most potent compound has a Ki’ value of 1 nM for InhA and MIC99 values of 1-3 μM for both drug sensitive and drug resistant strains of MTB. In addition to fatty acid biosynthesis, we are using structural and mechanistic approaches to characterize enzyme targets involved in the biosynthesis of the electron carrier menaquinone and the siderophore mycobactin, compounds that are essential for MTB viability. Current studies are focused on MenB, the dihydroxynapthoyl-CoA synthase in menaquinone biosynthesis, as well as MenF the first enzyme in this pathway which converts chorismate into isochorismate. The mechanism of MenF is being compared with that of MbtI, the first enzyme in the mycobactin pathway which converts chorismate into salicylate. Finally we are also studying the tubulin homolog FtsZ, which plays an essential role in mycobacterial cell division.

Professor Scott M. Sieburth (Temple University)
Scott Sieburth grew up in Rhode Island and graduated from Worcester Polytechnic Institute in 1977. He was awarded his Ph.D. from Harvard University after studying with Paul Wender there and at Stanford University. In 1982 he joined the Agricultural Chemicals Group of FMC Corporation in New Jersey. After seven years with FMC he moved to the State University of New York at Stony Brook where he was promoted to Associate Professor in 1996. In 2001 he moved to Temple University in Philadelphia where he continues to study organosilicon chemistry and biological activity, synthetic photochemical methods, and total synthesis.

Silicon as a Central Drug Design Component
Organosilanes can be incorporated into peptides and peptide-like molecules as a substituent (e.g., 1) or in a central position such as silanediol 2. Alpha-silyl amino acid derivatives 1 are relatively new and can suffer from hydrolytic instability in which the bond between silicon and the peptide chain is broken. Silanediols such as 2 are potentially unstable toward polymerization reactions (silicone formation). In both cases, stability is readily achieved by appropriate choice of the silicon environment. Recent advances in the preparation of 1 and 2, as well as applications of this chemistry toward biologically active molecules, will be described.
H N O Si O N H 1 O 2 H HO OH N Si O H N

Professor Nicole S. Sampson (Stony Brook University)
Nicole S. Sampson was born in Indianapolis, Indiana in 1965 and acquired her B.S. degree in chemistry at Harvey Mudd College in 1985. She obtained her Ph.D. in the laboratory of Paul A. Bartlett at UC Berkeley in 1990 and then carried out postdoctoral research in the laboratory of Jeremy R. Knowles at Harvard University. Nicole joined the faculty at Stony Brook University in 1993 and is currently a Professor of Chemistry, as well as a member of the graduate programs in Pharmacology, Biochemistry & Structural Biology, and Biophysics. Her research interests are in the areas of mechanistic enzymology and chemical biology. Her work presently focuses on catalysis by cholesterol–modifying enzymes, how they modify the lipid bilayer and their role in bacterial pathogenesis, investigating the role of protein segmental dynamics in catalysis, and probing protein–protein interactions in mammalian fertilization using synthetic molecules.

Multivalent and Stereoregular Polymers to Probe Fertilinβ Function in Fertilization
In the post-genomic era, understanding protein function is a critical focus of chemical biology research. The sperm protein fertilinβ, a member of the ADAM family of proteins is implicated in sperm-egg binding in all mam¬mals studied to date. The three-amino acid sequence ECD is the essential eggbinding element of fertilinβ. We present the synthesis and mechanistic investigation of polymers that display the ECD motif in multivalent fashion to probe fertilinβ-egg interactions.

Professor Steven Rokita (University of Maryland)
Steven E. Rokita (b.1957), Professor, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD. B.S., 1979, University of California at Berkeley; Ph.D., 1983, Massachusetts Institute of Technology (mentor: Christopher T. Walsh); NIH Postdoctoral Fellowship, 1984-1986, Rockefeller University (mentor: E. Thomas Kaiser). Catacosinos Young Investigator for Cancer Research, 1988. Molecular Biochemistry Advisory Panel, NSF 1993-1996; Bioorganic and Natural Products Study Section, NIH, 1997-2001. Advisory Board of Bioconjugate Chemistry, 1997-1999. Vice-Chair (1998) and Chair (1999), Bioorganic Chemistry Gordon Conference. Nominating Committee, Biological Chemistry Division, American Chemical Society, 2000. Alternative Councilor, Biological Chemistry Division, American Chemical Society, 2002- 2004. Awards (Univ. of Maryland) include Outstanding Invention (2001) and Faculty Excellence in Research (2005). Area of Research. Bioorganic/biochemistry. Nucleic acid structure and reactivity; target promoted alkylation of DNA, excess electron transfer in DNA; biological and biomimetic reactions of nickel and copper; enzyme mechanisms of dehalogenation.

Selective Alkylation of DNA through a Recognition-Dependent Process
Highly electrophilic quinone methides are generated during metabolism of numerous compounds ranging from food preservatives to anti-cancer drugs. These species readily alkylate the most nucleophilic sites of DNA. Reaction is reversible, however, and the major adducts act as a reservoir for continually regenerating quinone methides over an extended period. The consequence of this reversibility is evident in the evolution of DNA products generated by a simple model quinone methide as well as quinone methides that have been conjugated to DNA binding ligands. In particular, oligodeoxynucleotide-quinone methide conjugates appear to form instrastrand adducts with all nucleotides except for T. Intrastrand reaction remains reversible and yet is not sensitive to trapping by external agents such as non-complementary DNA, thiols or water. The alternative interstrand reaction is only observed after association with complementary DNA. Once the self-adduct spontaneously regenerates the quinone methide, further base pairing with the target strand is allowed. This additional recognition in turn inhibits reformation of the intrastrand self-adduct and promotes interstrand alkylation of the chosen target. This overall process represents a O type of safety catch mechanism for HO delivering a highly reactive intermediate to a precise target and may ultimately provide a general reversible self-adduct formation approach to gene specific reactions in vivo.

quinone methide regeneration and full target recognition

target promted alkylation of a chosen nucleobase sequence

Professor Cynthia J. Burrows (University of Utah)
Cindy Burrows studied physical organic chemistry at the University of Colorado (B. A. 1975) and Cornell University (Ph. D. with B. K. Carpenter, 1982) before becoming an NSF-CNRS postdoctoral fellow with Nobelist J.-M. Lehn in Strasbourg, France. From 1983-1995, she held the positions of Assistant through Full Professor of Chemistry at Stony Brook and was the western neighbor of the Ojima group. In 1995, she returned to the West, along with her husband (Prof. Scott Anderson) and triplets (now age 13), as Professor of Chemistry at the University of Utah. Research in the Burrows lab ranges from the identification of new heterocyclic compounds and the mechanisms by which they are formed during DNA oxidation to the investigation of the biological effects of these lesions on DNA replication and repair. Prof. Burrows has been a member of numerous editorial boards and review panels; she also served as Associate Editor of Organic Letters from its inception until 2002 and is currently Senior Editor of the Journal of Organic Chemistry. She is a Fellow of the AAAS and the recipient of the Robert Parry Teaching Award at the University of Utah; her research was recently recognized with the ACS Utah Award and the U of U’s Distinguished Creative and Scholarly Research Award.

Heterocyclic Chemistry leading to Mutagenesis via Oxidation of DNA Bases
DNA in under constant assault by reactive oxygen species generated endogenously as a byproduct of respiration and exogenously under conditions of oxidative stress or radiation. Prolonged oxidative stress forms part of the etiology of cancer, atherosclerosis, neurological diseases and aging. The guanosine heterocycle is a principal target of oxidation leading to 8-oxoguanosine as well as newly characterized spirocyclic and guanidinium-derived products. The latter products have been the subject of some controversy concerning structural characterization and mechanism of formation, and the use of 13C, 15N, and 18O labeling has helped resolve some of these issues. Clues to the mechanism of formation have suggested parallel pathways for elucidation of adducts formed in oxidative polyamine and protein cross-linking to DNA. Synthetic methods for generation of new DNA lesions permit biochemical studies of DNA polymerases and DNA repair enzymes. These studies, in conjunction with in vivo mutagenesis analysis, suggest that these unusual oxidation products of guanosine may be highly detrimental to the integrity of the genome due to the formation of unusual base pairs that proliferate and escape repair.

Professor Glenn D. Prestwich University of Utah
Dr. Prestwich graduated with a B.Sc. (Honors) in Chemistry from the California Institute of Technology in 1970, he earned a Ph.D. in Chemistry from Stanford University in 1974, followed by three years as an NIH postdoctoral fellow, first at Cornell University and then at the International Centre for Insect Physiology and Ecology in Nairobi, Kenya. From 1977 to 1996, he was at The University at Stony Brook in New York, as Professor of Chemistry, Professor of Biochemistry & Cell Biology, and Director of the New York State Center for Advanced Technology in Medical Biotechnology. He co founded Clear Solutions Biotechnology, Inc. (Stony Brook, New York) to commercialize hyaluronan biomaterials. He is a recipient of Alfred P. Sloan Research and Dreyfus Teacher-Scholar Awards, and was honored with the 1998 Paul Dawson Biotechnology Award of the American Association of Colleges of Pharmacy. He was elected as a Fellow of the American Institute for Medical and Biological Engineering in 2005 and was selected as a V100 Top 100 Venture Entrepreneurs in Utah in 2005.

Injectable synthetic extracellular matrix for tissue engineering and repair
We recently developed a novel approach to the creation of a fully synthetic, covalently crosslinked extracellular matrix (sECM). This material may be crosslinked in situ in the presence of cells to provide an injectable cell-seeded hydrogel for tissue repair, or with drugs in a controlled-release format. Chemical modification of hyaluronan (HA), other glycosaminoglycans (GAGs), proteins, or other carboxylate-containing polymers with thiol residues creates macromonomers that can be crosslinked with biocompatibile polyvalent electrophiles. In the first section of this overview, we present the vision and strategy for creating sECMs. In the second section, we highlight selected in vitro and in vivo applications of this technology. Among the applications, we first show in vitro and in vivo growth of healthy cellularized tissues using films, sponges, and hydrogels based on the sECM technology. We then extend the use of the in situ crosslinkable sECM to the growth for the in vivo repair of cartilage defects and healing of tympanic membrane perforations. Next, we describe the use of biointeractive, crosslinked heparin-containing GAG dressings for controlled release of bFGF and re-epithelialization of full-thickness wounds in a diabetic mouse model of chronic wound healing. Finally, we illustrate the use of in situ crosslinkable HA hydrogels, with and without covalently linked antiproliferatives, for prevention of abdominal surgical adhesions and maintenance of sinus ostia in vivo.

Dr. Scott D. Kuduk (Merck Research Laboratories, PA)
Scott Kuduk was born in Long Island, NY. He obtained his B.S. and Ph.D. degrees at the State University of New York Stony Brook under the guidance of Professor Iwao Ojima. He joined the Merck Research Laboratories in 1999 after completing postdoctoral studies with Professor Samuel Danishefsky at the Sloan-Kettering Institute for Cancer Research. He is currently a Research Fellow at Merck where his research has dealt with organofluorine chemistry and with the design of novel therapeutic agents for the treatment of pain.

2,3-Diaminopyridine Bradykinin B1 Receptor Antagonists
The quest for improved treatments of chronic pain and inflammation continues to be an area of intense research. Human bradykinin B1 receptor antagonists embody a novel approach for the treatment of these disease states. A series of 2,3-diaminopyridine based BK B1 receptor antagonists was optimized to have sub-nanomolar affinity for the human B1 receptor and good pharmacokinetic properties. The optimization was achieved by blocking a number of potential metabolic pathways, particularly through the use of various ester isosteres. Lead compounds were shown to exhibit good efficacy in rabbit in vivo models of pain and inflammation.
R1 H N O N NH CO2Me N H N O NH R3 R2


Dr. An T. Vu (Wyeth Research, PA)
An Vu was born and raised in Saigon, Vietnam. During his youth, he emigrated along with his parents to the United States and settled in a small town in Georgia where he continued his secondary education. In 1992 he obtained his B.S. in Chemistry from Mercer University in Macon, GA. He received his Ph.D. in Organic Chemistry in 1997 from Emory University in Atlanta, GA, where he studied the transition metalmediated reductive cyclization reactions under the direction of Professor William E. Crowe. He then worked with Professor Iwao Ojima as an NIH Postdoctoral Research Fellow at the State University of New York at Stony Brook, where he developed useful catalytic synthetic processes involving rhodium-catalyzed silylcarbocyclization (SiCaC), heterosilylcarbocyclization and silylcarbotricyclization (SiCaT) reactions. In 1999 he joined Wyeth Research in Collegeville, PA where he is currently a Senior Research Scientist and working in the areas of women’s health, cardiovascular and metabolic diseases. He is the author of a number of scientific articles, book chapter, abstracts, presentations, and patent publications.

2-Phenylquinolines as Potent and Selective Estrogen Receptor beta (ERβ) Ligands.
The discovery in 1996 of a second subtype of estrogen receptor, estrogen receptor beta (ERβ), with its unique tissue distribution patterns and transcriptional properties from those of ERα, has prompted intense research to elucidate its physiological functions and identify its potential therapeutic targets. Our approach toward this goal has been to utilize highly selective ERβ agonists. Recently, we have designed and developed a series of 2-phenylquinolines as a new class of ERβ selective ligands. A number of substituted 2-phenylquinolines displayed low nanomolar affinity and as high as 100 fold ERβselectivity. A select group of compounds were profiled as either full or partial ERβ agonists in a cell-based functional assay measuring the transcription of KRT19 mRNA. The uterine weight estrogenic bioassay of the most selective compounds showed no significant uterine stimulation, thus indicating no activation of ERα in this sensitive estrogen target organ. The design, synthesis, biological evaluation, and potential binding modes within the ligand binding pocket of this class of compounds will be discussed.

R1 R6 N HO R5 R4 R3 OH R2

Professor Thierry Brigaud (Université de Cergy-Pontoise, France)
Born 16 August 1962 in Paray-le-Monial (France). Ph.D in organic chemistry in 1990 at the Université Claude Bernard, Lyon I (France) under the direction of Prof. E. Laurent: Nucleophilic fluorination in αposition of an aromatic ring or a thioether. Postdoc at the State University of New York at Stony Brook (USA) in 1990-1991 under the supervision of Prof. I. Ojima : Asymmetric synthesis of non-protein amino acids. In 1991, appointed maître de conférences of the Université de Reims Champagne-Ardenne (France). From 2002, appointed professor of the université de Cergy-Pontoise (France). Main domain of interest: Organofluorine chemistry, asymmetric synthesis, Synthesis of fluorinated analogs of natural products (carbohydrates, terpenes, amino acids).

Chiral fluorinated imines and oxazolidines: synthons for organofluorine chemistry and asymmetric synthesis
Fluorinated imines, hydrazones and oxazolidines derived from chiral amino alcohols are very useful synthons for the stereoselective synthesis of  -fluoroalkylated amino compounds.1,2 The Strecker and the Mannich-type reactions with chiral fluorinated iminium constitute a powerful method for the synthesis of enantiopure fluorinated   and  -amino acids,  -amino ketones, amino NH2 alcohols and diamines in a few steps.
F3C CO2H R1 NH2 O F3C R α-amino acids N F3C or H N F3C R O R1 NH2 F3C R


R2-M ou R2SiMe3 F3C NH2 R1 R

β-amino acid and ketones NH2 F3C R



Diamines NH2 OH OH F3C


Recent results about the use of fluorinated oxazolidines as chiral auxiliaries will also be presented. The oxazolidines derived from fluoral hemiacetal and (R)-phenylglycinol are very stable to hydrolysis. Therefore these oxazolidines can be used as highly efficient chiral auxiliaries for amide enolates alkylation.
R F3C O O N Ph 1) Base 2) R'X R R' F3C O N O High diastereoselectivity Ph

Amino alcohols

(1) Lebouvier, N.; Laroche C., Huguenot, F.; Brigaud, T. Tetrahedron Lett. 2002, 43, 2827. (2) Fries, S.; Pytkowicz, J.; Brigaud, T. Tetrahedron Lett. 2005, 46, 4761.

Dr. Joseph Zhu (Amgen, Inc., )
Joseph (Jiawang) Zhu, Ph.D. is currently a Senior Scientist in the Department of Chemistry Research & Discovery at Amgen, Inc. His research interests are design and syntheses of biologically and therapeutically interesting molecules, and studying their pharmacokinetics, pharmacodynamics, and other properties. He has published more than 10 articles and co-authored more than 10 patents. He holds a B.S. in Chemistry from Nanjing University, China, and a Ph.D. in Chemistry from Colorado State University at Fort Collins under the supervision of Professor Louis S. Hegedus, and Pursued Post-doc research in Professor Iwao Ojima’s laboratories at SUNY-Stony Brook.

Design and Synthesis of Conformationally Constrained TRPV1 Antagonists
The vanilloid receptor-1 (VR1 or TRPV1) belongs to the family of transient receptor potential (TRP) cation channels and is activated by heat, acid, and plant irritants such as capsaicin. TRPV1 is predominantly expressed in primary sensory neurons and is involved in the transmission process of noxious pain stimuli to the brain. Blockade of the cell signaling with a TRPV1 antagonist offers a potential for the development of novel analgesics. Recently, we have discovered and reported a series of N-aryl cinnamides as potent, selective, and competitive TRPV1 antagonists. Probing the antagonist-binding pocket of TRPV1 via studies of its ligands of (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamides have lead to the hypothesis of that the bioactive conformations, the receptor-binding modes, of the N-aryl cinnamides are the co-planar, s-cis conformation with respect to the carbonyl group. The synthesis, conformational analysis, and biological properties of these analogs will be presented. Furthermore, the synthesis and biological activities of conformationally constrained pharmacophores will be addressed.

Dr. Matthew M. Zhao (Merck Research Laboratories, NJ)
Born in 1965, Xingtai, Hebei Province, China. He obtained his BS in chemistry from Lanzhou University in 1985. He was awarded CGP scholarship in 1986 to pursue graduate study in the US. He joined professor Ojima’s group in 1987 and obtained his PhD degree in 1991. He then went on to Professor Leo Paquette group for postdoctoral research and was awarded Merck Postdoctoral Fellowship. He joined Process Research Department in Merck Research Laboratories in 1993 focusing on the development of efficient, robust and environmentally benign process for the production of novel Merck drug candidates. He has worked on numerous projects highlighted by the development of manufacture processes for two successful Merck drugs, Singulair® and Emend®. He has over 25 publications and hold more then ten patents. He is currently a Senior Research Fellow.

Development of the Manufacturing Process to Emend® (Aprepitant), Winner of 2005 Presidential Green Chemistry Challenge Award
Aprepitant (1), an antagonists of the neurokinin-1 (NK-1) receptor is a new therapeutic agents for the treatment of chemotherapy-induced emesis. The first generation synthesis allowed us to made multikilogram quantities of the drug substance. Search for better alternatives synthesis of aprepitant ultimately lead to discovery of a much more efficient manufacturing route with over 80% reduction in cost, energy and raw material volumes.




CF3 F 1

Dr. Ivan Habuš (Ruđer Bošković Institute, Croatia)
Ivan Habus, Associate Professor, Rudjer Boskovic Institute (RBI, Zagreb, Croatia), Division of Physical Chemistry, Laboratory for Analytical Chemistry – Head of the Laboratory. He was born in 1956 and received his Ph.D. in 1988 at RBI. Research project was involved in the transformations of monosaccharides into new chiral bidentate ligands, bis-diphenyl-phosphinites and phosphines, and development of their rhodium(I) complexes as the catalysts for the homogeneous catalytic hydrogenation of various prochiral substrates. From 1988 to 1990 he was engaged in postdoctoral research with Prof. Iwao Ojima at SUNY at Stony Brook, NY, USA. He was involved in asymmetric synthesis of various non-protein amino acids by applying “β-Lactam Synthon Method”. From 1990 to 1992 he spent with Prof. Francis Johnson as postdoctoral fellow at SUNY at Stony Brook. At Hybridon, Inc., Cambridge, MA, USA, he was appointed as research scientist (1992-1997) and senior research scientist (1997-1998) in the field of oligonucleotide synthesis. From 1998 to 2000 he was employed as principal scientist at ArQule, Inc., Woburn, MA, USA, working in the field of combinatorial chemistry. Currently at RBI, he is supervising the custom service activities: Organic Elemental Microanalysis (C, H, N, S, halogens) and FT-IR Spectroscopic Analysis of Urinary/Gall Calculi. Based on the analysis of urinary calculi in the Laboratory is followed the presence of urolitiase in the Republic of Croatia dependent on region, sex, and age of the patients.

Diels-Alder reactions on imines derived from 3-amino-β-lactams
Synthesis of diversily substituted monocyclic β-lactams have been of considerable interest to the synthetic community in the past few decades [1]. Because of the recent developments using β-lactams as synthons for several biologically active compounds, research on this topic has gained tremendous attention [2,3]. Hetero Diels – Alder reactions involving imino-dienes or imino-dienophiles are widely used for the construction of nitrogen-containing compounds [4,5]. Our interest in the use of 3-amino-βlactams [6,7] as starting substrates for the preparation of potentially bioactive products prompted us to evaluate the combination of the aza-Diels – Alder reaction of 2-azetidinone-tethered imines I with siloxydienes as a route to the asymmetric synthesis of 5,6-dihydro-γ-pyridones II using β-lactams as chiral building blocks (Scheme 1) [8,9]. Effects of various dienes and substituents on dienophile, Lewis acids, and solvents on the product formation and diastereoselectivity of the reactions will be discussed.
R3 R2 OTMS O R3 N R2 N N O R3 R2

N O R1


Lewis acid CH3CN, -20 oC

N O R1 O II R1 = H, Aryl R2 = Fc, Aryl R3 = Fc, Aryl, Alkyl N R1

I R1 = H, Aryl R2 = Fc, Aryl R3 = Fc, Aryl, Alkyl

1. G.S. Singh, Tetrahedron, 59 (2003) 7631. 2. H.C. Neu, Science, 257 (1992) 1064. 3. A.K. Bose, B.K. Banik, C. Mathur, D.R. Wagle, M.S. Manhas, Tetrahedron, 56 (2000) 5603. 4. P. Buonora, J.-C. Olsen, and T. Oh, Tetrahedron, 57 (2001) 6099. 5. K.A. Jorgensen, Angew. Chem. Int. Ed., 39 (2000) 3558. 6. I. Ojima and I. Habuš, Tetrahedron Lett., 31 (1990) 4289. 7. I. Habuš et al., J. Mol. Struct., (2005). 8. J.F. Kerwin, Jr. and S. Danishefsky, Tetrahedron Lett., 23 (1982) 3739. 9. B. Alcaide, P. Almendros, J.M. Alonso, and M.F. Aly, Chem. Eur. J., 9 (2003) 3415.

Dr. Masakatsu Eguchi (Institute for Chemical Genomics, WA)
Masakatsu Eguchi received his B.S. degree in 1981 and M.S. degree in 1983 in pharmaceutical science from Tokyo College of Pharmacy (now Tokyo University of Pharmacy and Life Science). His Ph.D. degree was granted from Brigham Young University, department of chemistry in 1990, where he worked under the late Prof. Bryant Rossiter. Subsequently, he did postdoctoral work at State University of New York at Stony Brook with Prof. Iwao Ojima ('90-'93) and Sandoz (now Novartis). In 1994, he joined Molecumetics Ltd. as a senior scientist and was promoted to senior research fellow in 1999 working on the design and combinatorial synthesis of peptidomimetics. He moved to Pacific Northwest Research Institute as a staff scientist with Prof. Michael Kahn in 2000. In 2004, Prof. Kahn's research group established a new nonprofit research organization, Institute for Chemical Genomics. Masa has been actively involved in drug discovery efforts for 10 years.

Design, Synthesis, and Application of Peptide Secondary Structure Mimetics
Secondary structure elements in proteins play a key role in molecular recognition events in biological systems through their characteristic three-dimensional presentation of functional groups on their surfaces. Cytokine-receptor interaction and many protein-DNA interactions are mediated through αhelical structure, many peptide ligand-receptor interactions and antigenantibody interactions are mediated through reverse turns, and proteases, kinases, most SH2 domains, and MHC recognize their substrates through β-strand structures. Most of these proteinprotein interactions are initiated or mediated by a key local secondary structure element in the protein; therefore, small molecules bearing a similar local structural feature can effectively mimic the ligand binding function of a protein or peptide. A successful peptidomimetic must be able to present the correct pharmacophoric residues in the proper three-dimensional space. Conformationally constrained analogs of such peptidomimetics pay a lower entropy cost upon binding to their receptor or enzymes. The rapid generation of secondary structuretemplated chemical libraries through solid-phase synthesis is a key technology to develop novel pharmaceutical agents effectively. We have developed β-turn and β-strand scaffolds readily accessible through solid phase synthesis from commercially available diversity components and applied these scaffolds for the preparation of biologically active compounds such as protease inhibitors, opioid receptor agonists, or transcription factor modulators. Design and synthesis of these chemical libraries and some preliminary biological data will be presented.

Professor Elke Schoffers (Western Michigan University)
Prof. Schoffers started her academic career at the Johannes Gutenberg University in Mainz, Germany, and continued graduate studies in the United States under the supervision of Professors I. Ojima (SUNY Stony Brook, M.S., 1991), C.R. Johnson (WSU, Ph.D., 1996), and A.J. Pearson (CWRU, postdoc, 1996-98). Her expertise is in the area of stereoselective synthesis with background in organometallic, heterocyclic, and biochemistry. Specific projects address the development of N-containing ligands for asymmetric catalysis and the synthesis of metabolites that influence biological signals. This includes the preparation of inosamines that have been proposed to be nutritional mediators for nitrogen fixation in legume plants. Over the last 5 years, Professor Schoffers has worked with 7 graduate and 9 undergraduate students (8 female, 2 minorities) on various research projects.

Looking for a Ligand with a New Twist? Chiral Phenanthrolines for Organic Chemistry
1,10-Phenanthroline has long been known for its complexes with metals and non-metals and has thus found numerous applications in analytical chemistry since the 1930’s. More recently, there has been a renewed interest in 1,10-phenanthroline and its derivatives for their potential applications in asymmetric catalysis.
O O N Ph Ph NH HN Ph



N (1)


N (2)


(1,10-Ph en)

Herein we report our progress towards functionalizing the 1,10-phenanthroline template, and give details about the preparation and application of novel optically active derivatives (1, 2). Among others, we tested these new ligands in asymmetric alkylation, aminohalogenation, reduction and Aldol reactions

Biomedical innovation Through Multidisciplinary and Translational Research – From Bench to Bed Side –