1.

INTRODUCTION

Nitrogen containing compounds, which are classified as amines, are found widely in nature. These compounds posses numerous biological activities which are beneficial to the pharmaceutical, chemical and agricultural related industries. The five member nitrogencontaining heterocycles exists in many natural plants, microorganism and also in synthetic drugs. For example, bleomycin, lactacystin. These natural compounds have either proline, hydroxyproline , pyrrolidinone (2,4 Pyrrolidinone) or prolinol rings. Lately these compounds have received much attention due to their diverse medicinal properties namely as anti bacterial, antifungal, anti bacteria ,antivirus.
O O N H

2,4 Pyrrolidinone

2.

PROBLEM STATEMENT OF THE STUDY

The existing natural resources are not sufficient to cope with the demand from the industries and society. In addition, the demand of a more efficient synthetic strategy that involves less steps, high yields and stereo controlled reactions procedure is also increasing. Therefore, studies on the exploration of new synthetic strategy and understanding of chemical mechanism involved are crucial to solve these problems.

4-Michael adducts via Michael addition reaction . are significant key intermediates for the synthesis of several natural pyrrolidine type compounds such as the antihypertensive antibiotic codonopsinine[2] and antifungal agent preussin[3]. Many research teams had anticipated in employing nitrogen nucleophiles in their respective conjugate addition reactions[7]. 2-pyrrolidones.3 To transform 3-pyrrolin-2-ones to their respective 1. OBJECTIVES OF THE STUDY 4. cycloaddition of achiral nitrile oxide and formation of hydrazone derivatives[4] has successfully synthesized. epoxidation and cycloaddition[6]. stereoselective ketone reduction. and nitrogen nucleophiles. In addition.3. REVIEW OF THE PREVIOUS STUDIES Pyrollin-2-ones and 2-pyrorolidones are moieties often found in the structures of many biologically active natural products[1].2 To perform epoxidation and subsequently oxirane ring-opening reaction on 3pyrrolin-2-ones 4. we encountered with the need of an α. not much work has been reported on the chemistry of 3-pyrrolin-2-one ring moiety via C-C bond formation.β-unsaturated-γ-lactam ring system as our essential advanced intermediate toward bioactive natural constituent.1 To synthesize 3-pyrrolin-2-ones via a five step synthetic approach 4. N-protection. A series of of novel pyrrolidinone ring units which has undergone various chemical transformation which include alkylation. enolates. decarboxylation. compounds with such 3-pyrrolin-2-one ring system can be valuable starting material in organic synthesis due to its ability to react as an acceptor in conjugate addition of organocuprates. however.[5] While synthesizing the hypotensive drug. Some of these pyrrolidinone-derived compounds were confirmed to exhibit neuroprotective ability via the hydrogen peroxide oxidative stress-induced model and against a normal and cancer cell lines. 4. particularly. codonopsinine. acylation.

polyleucine. demthoxycarbonylation.β-unsaturated-γ-lactam. r. is outlined in Scheme 1 below: O Me O O NH2 K+ -O O O O Me R2 O Condensation HN O OCH3 OCH3 R2 Methyl esters of amino acid methyl malonate potassium OCH3 Dieckman cyclization O O N H O R2 Decarbomethoxylation O N H O R2 R2 = -H -CH3 Reduction O N H OH R2 Elimination and Protection O O N O R2 Scheme 1: Synthesis of C5-substituted 3-pyrrolin-2-ones Epoxidation Epoxidation can be performed as follows: Epoxidation protocols O N R1 R2 via standard peroxidants O O + N R1 R2 O N R1 R2 O Scheme 2: Epoxidation of synthesized 3-pyrrolin-2-ones Possible reagents and reaction conditions will be employed for epoxidation: 1) H2O2. Dieckmann cyclization. CH2Cl2. elimination and protection of N-Boc. CH2Cl2. .t. H2O.t. The methodology towards the preparation of the proposed. 2) m-CPBA.5. 3) Dimethyldioxirane. acetone.t. r. reduction. 3-pyrrolin-2-ones will be prepared in a five-step synthetic approach of condensation. METHODOLOGY Synthesis of 3-pyrrolin-2-ones α. r.

4-conjugate addition protocols O N R1 R2 via Michael Addition O N R1 R3 R2 Scheme 5: Michael Addition reactions of 3-pyrrolin-2-ones Possible reagents such as CH2(COOR)2 and reaction conditions will be employed : 1) K2CO3. 2) MeLi. r. -80oC 6.2 Generating potential precursors for the synthesis of bioactive natural compounds . SIGNIFICANCE OF STUDY 6. as well as Gilman and Grignard-cuprates reagents. ether. 1.1 Exploring diverse synthetic knowledge and chemical possibilities 6.Michael Addition Reaction Different approach via Michael Addition conjugate type reaction will also be explored by using methylene compounds in the presence of potassium carbonate. CuI. ether/acetonitrile.t.

.. A. University Kebangsaan Malaysia.E63.. 02941-o2942 (b) Mohammat. A. Zurina Shaameri.. Org.o661-o662. F. Proceedings of the 21st Annual Seminar of the Malaysia Natural Products Society. 6979-6981 iii. 2004. Acta Cryst E. Chantrapromma. Z. Tetrahedron Lett. 2007. M.O. (g) Hamzah. M. Acta Cryst E.F. A. Acta Cryst E.R. Z. ISBN 978-983-43150-54.. Chem.. 2006. deOca. 1998. Santana. (b) Gurjar... R.REFERENCES i.A. Chem...F.o457-o458. Kamarulzaman. Hamzah.o1795-o1797. vii. M.4]non-2-ene-7.L.” Herbal Medicine: Nature’s gift for health.K... J.8-dimethyl-1oxa-2.G.. Deng.M... Reddy. V.8974-8976 ii. 9. 17. M. ARKIVOC. N. A.P. Prakash. Franco...2005. Sect.2007. Tetrahedron : Assymetry. Shaameri..S.. Acta cryst E. M.C. (a) Yaser Bathich. F. 5111-5115 iv. 1050.B.. V.. A. J. 2009 “6-Benzyl-3-(1. Y. Shaameri. C.1380-1386. Saritha.-O. Castillo. Radom.. Tetrahedron Asymetry.S.S.M..S. A. (b) Davis.. Corey.9-dione”. B. P. M..K.L. Bathich. 60. J. Fournier.V.E64. (a) Chandrasekar. Jagadeshwar.. (a) Garcia. 47.J. E..D. J-F. Shaameri. Tetrahedron. Sazali. S.H...L. (a) Najim.. 2006. East.6-diazaspiro[4. xii. (b) Shaameri.N. 2010. H..J.S. Hoong-Kun Fun. Correia.S. (a) Caldwell..A.L. Reddy..J.. M. Ching Kheng Quah.70. Molecules. 2008. (b) Langlois. B. Borhade. Z. D...8037-8040 ... Craig. Hamzah. Tetrahedron Lett. (2008) “Synthetic Studies and Biological Activity of some Pyrrolidinone Type Compounds. Madeleine Joullie.2005.38. Ahmad Sazali Hamzah.E. J. S.. 1759-1769.S. 303-312 vi. Am.J. Soc. Merino.S..J. Fun.H. 2006.. E65.C. merchant. M. 1997.S.. Fun.R.67-90.. N..G. (e) Mohammat.. S.4-dioxaspiro[4.S.V. Calvez. dosSantos. Chantrapromma.5]decan-2-yl)-8. Z.. B. A. Sazali. Hamzah. 15. Z. Mat Zain.Yamin. C..E63. ISSN 1424-6376. Puranik..K. v. 127(25).. A.G. Issue of honour of Prof. H. Carpes. Ramana.. Shaameri.. 9340-9353. C.

Sign up to vote on this title
UsefulNot useful