Penicillin

Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi, including penicillin G, procaine penicillin, benzathine penicillin, and penicillin V. Penicillin antibiotics are historically significant because they are the first drugs that ere effective against many previously serious diseases, such as syphilis, and infections caused by staphylococci and streptococci. Penicillins are still idely used today, though many types of bacteria have no become resistant. !ll penicillins are "#lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram#positive organisms.

Fig: Penicillin

Synthesis
Principle
$here are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin). $he first step is the condensation of three amino acids%&#'#aminoadipic acid, &# cysteine, &#valine into a tripeptide. (efore condensing into the tripeptide, the amino acid &#valine must undergo epimerization to become )#valine. $he condensed tripeptide is named *#(&#'#aminoadipyl)#&#cysteine#)#valine (!CV). $he condensation reaction and epimerization are both catalyzed by the enzyme *#(&#'# aminoadipyl)#&#cysteine#)#valine synthetase (!CV+), a nonribosomal peptide synthetase or N,P+. $he second step in the biosynthesis of penicillin G is the o-idative conversion of linear !CV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (.PN+), hich is encoded by the gene pcbC. .sopenicillin N is a very ea/ intermediate, because it does not sho strong antibiotic activity. $he final step is a transamidation by isopenicillin N N#acyltransferase, in hich the '#aminoadipyl side#chain of isopenicillin N is removed and e-changed for a

phenylacetyl side#chain. $his reaction is encoded by the gene pen)0, uni1ue in the process of obtaining penicillins.

hich is

Reaction

Fig: +ynthesis of Penicillin

Application
2. Penicillin is an antibiotic and is used to treat and prevent a variety of bacterial infections.

Biotin
(iotin, also /no n as vitamin 3 or coenzyme ,, is a (vitamin (4). ater#soluble (#vitamin

.t is composed of a ureido (tetrahydroimidizalone) ring fused ith a tetrahydrothiophene ring. ! valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. (iotin is a coenzyme for carbo-ylase

enzymes, involved in the synthesis of fatty acids, isoleucine, and valine, and in gluconeogenesis. $he only human health condition, for hich there is evidence of biotin5s potential benefit as a treatment, is biotin deficiency. $he chemical structure of (iotin is#

Fig: (iotin

Synthesis
Principle
(iotin is a heterocyclic, +#containing monocarbo-ylic acid. .t is made from t o precursors, alanine and pimeloyl#Co! via three enzymes. 6#!mino#4#o-opelargonic acid synthase is a pyrido-al 75#phosphate enzyme. $he pimeloyl#Co!, could be produced by a modified fatty acid path ay involving a malonyl thioester as the starter. 4,6)iaminopelargonic acid ()!P!) aminotransferase is unusual in using +# adenosyl methionine (+!8) as the N39 donor. )ethiobiotin synthethase catalyzes the formation of the ureido ring via a )!P! carbamate activated ith !$P. (iotin synthase reductively cleaves +!8 into a deo-yadenosyl radical%a first radical formed on dethiobiotin is trapped by the sulfur donor, hich as found to be the iron#sulfur (:e#+) center contained in the enzyme.

Reaction

Fig: +ynthesis of (iotin

Application
2. (iotin is used for preventing and treating biotin deficiency associated pregnancy, long#term tube feeding, malnutrition, and rapid eight loss. ith

9. .t is also used orally for hair loss, brittle nails, s/in rash in infants (seborrheic dermatitis), diabetes, and mild depression. ;. (iotin is essential for your metabolic process. $his vitamin processes nearly every type of food that is ingested, including carbohydrates, protein and fat.

Podophyllotoxin
Podophylloto-in is a non#al/aloid to-in lignan e-tracted from the roots and rhizomes of Podophyllum species. .t is present at concentrations of <.; to 2.<= by mass in the rhizome of !merican 8ayapple (Podophyllum peltatum). !nother common source of podophylloto-in is the rhizomes of Podophyllum he-andrum ,oyle ((erberidaceae) Podophylloto-in bears a four consecutive chiral centers, labelled C#2 through C#>. $he molecule also contains four almost planar fused rings. :our ends of podophylloto-in have o-ygen atoms at the functional groups dio-oles, metho-ys, lactone, and secondary alcohol. $he structure is given belo #

Fig: Podophylloto-in

Synthesis
Principle
.t is synthesized from coniferyl alcohol being converted to (?)#pinoresinol in the presence of a one#electron o-idant through dimerization of stereospecific radical intermediate. Pinoresinol is subse1uently reduced in the presence of co#factor N!)P3 to first lariciresinol, and ultimately secoisolariciresinol. &actonization on secoisolariciresinol gives rise to matairesinol. +ecoisolariciresinol is assumed to be converted to yatein through appropriate 1uinomethane intermediates, leading to podophylloto-in.

Reaction

Fig: +ynthesis of Podophylloto-in

Application
2. Podophylloto-in displays a range of activities such as cathartic, purgative, antiviral, vesicant, and antihelminthic. 9. Podophylloto-in is the pharmacological anticancer drug etoposide. precursor for the important

;. .t is used on the s/in as a topical treatment of e-ternal genital arts, caused by some types of the human papillomavirus (3PV), and other arts.

Caffeine
Caffeine (C632<N>@9) is the common name for trimethyl-anthine (systematic name is 2,;,4#trimethyl-anthine or ;,4#dihydro#2,;,4#trimethyl#23#purine#9,A#dione). $he chemical is also /no n as coffeine, theine, mateine, guaranine, or methyltheobromine. Caffeine is naturally produced by several plants, including coffee beans, guarana, yerba matB, cacao beans, and tea. :or the plants, caffeine acts as a natural pesticide. .t paralyzes and /ills insects that attempt to feed on the plants. $he chemical structure is given belo #

Fig: Caffeine

Synthesis
Principle
Caffeine can be synthesized from )imethyl#uric acid. )imethyl#uric acid treated ith trichloride and o-ychloride of phosphorus at 27<CC to produce Chlorotheophylline. .n the process, a hydro-yl group is replaced by one chlorine atom. 3ydriotic acid used to reduce chlorotheophylline into theophylline. $hen, methyl iodide and theophylline react to produce caffeine.

Reaction

Fig: +ynthesis of Caffeine

Application
2. Caffeine is a psychoactive (mind#affecting) drug that serves as a stimulant. 9. Caffeine is a mild diuretic. ;. Caffeine is used in headache medications.

Nicotine
Nicotine is a potent parasympathomimetic al/aloid found in the nightshade family of plants (+olanaceae) and a stimulant drug. .t is a nicotinic acetylcholine receptor agonist. .t is made in the roots and accumulates in the leaves of the plants. .t constitutes appro-imately <.AD;.<= of the dry eight of tobacco and is present in the range of 9D4 EgF/g of various edible plants. .t functions as an antiherbivore chemicalG therefore, nicotine as idely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently idely used.

Fig: Nicotine

Synthesis
Principle $he biosynthetic path ay of nicotine involves a coupling reaction bet een the t o cyclic structures that compose nicotine. 8etabolic studies sho that the pyridine ring of nicotine is derived from niacin (nicotinic acid) hile the pyrrolidone is derived from N#methyl#H2#pyrrollidium cation. (iosynthesis of the t o component structures proceeds via t o independent syntheses, the N!) path ay for niacin and the tropane path ay for N#methyl#H2#pyrrollidium cation. $he N!) path ay in the genus nicotiana begins ith the o-idation of aspartic acid into '#imino succinate by aspartate o-idase (!@). $his is follo ed by a condensation ith glyceraldehyde#;#phosphate and a cyclization catalyzed by 1uinolinate synthase (I+) to give 1uinolinic acid. Iuinolinic acid then reacts ith phosphoribo-yl pyrophosphate catalyzed by 1uinolinic acid phosphoribosyl transferase (IP$) to form niacin mononucleotide (Na8N). $he reaction no proceeds via the N!) salvage cycle to produce niacin via the conversion of nicotinamide by the enzyme nicotinamidase. $he N#methyl#H2#pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane#derived al/aloids. (iosynthesis begins ith decarbo-ylation of ornithine by ornithine decarbo-ylase (@)C) to produce putrescine. Putrescine is then converted into N#methyl putrescine via methylation by +!8 catalyzed by putrescine N#methyltransferase (P8$). N#methylputrescine then undergoes deamination into >#methylaminobutanal by the N#methylputrescine o-idase (8P@) enzyme, >#methylaminobutanal then spontaneously cyclize into N# methyl#H2#pyrrollidium cation. $he final step in the synthesis of nicotine is the coupling bet een N#methyl#H2# pyrrollidium cation and niacin. !lthough studies conclude some form of coupling bet een the t o component structures, the definite process and mechanism

remains undetermined. $he current agreed theory involves the conversion of niacin into 9,7#dihydropyridine through ;,A#dihydronicotinic acid. $he 9,7#dihydropyridine intermediate ould then react ith N#methyl#H2#pyrrollidium cation to form enantiomerically pure (D)#nicotine. Reaction

Fig: +ynthesis of Nicotine

Application
2. .t is an aid to smo/ing cessation, sometimes /no n as nicotine replacement therapy (N,$). 9. .t is used to provide relief from the unpleasant ithdra al symptoms and to reduce the craving for nicotine that one gets hen he or she tries to stop smo/ing. ;. Nicotine as idely used as an insecticide.