Asymmetric synthesis FOR BSc, MSc, Bpharm, M,pharm

Asymmetric synthesis FOR BSc, MSc, Bpharm, M,pharm

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  SHIKHA D. POPALI HARSHPALSINGH WAHI GURUNANAK COLLEGE OF PHARMACY, NAGPUR
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  Introduction  The directsynthesis of an optically active substance from actively inactive substance(compound) with or without the use of optically active reagents is called as asymmetric synthesis.  Production of a specific enantiomer from achiral compound or racemic mixture.  A laboratory synthesis of a chiral compound from achiral or racemic starting materials alone always gives a racemic mixture of enantiomers.  If you want to make just one enantiomer, you have to use a starting material or reagent which is also just one enantiomer. 2
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  CHIRAL POOL SYNTHESIS simplest and oldest approaches for enantioselective synthesis,  Uses an enantiomerically pure natural product as a starting material,  The chiral pool—Nature’s ‘ready-made’ chiral centres :pure natural products, usually amino acids or sugars, from which pieces containing the required chiral centres can be taken and incorporated into the product.  Aspartame from s- phenylanine and s- aspatic acid. 3
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  CHIRAL AUXILIARIES  Anenantiomerically pure compound (usually derived from a simple natural product like an amino acid), called a chiral auxiliary, is attached to the starting material.  A diastereoselective reaction is carried out, which, because of the enantiomeric purity of the chiral auxiliary, gives only one enantiomer of the product.  The chiral auxiliary is removed by, for example, hydrolysis, leaving the product of the reaction as a single enantiomer.  The best chiral auxiliaries can be recycled, so although stoichiometric quantities are needed, there is no waste. 4
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  Flow chart ofthe chiral auxiliary strategy 5
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   An example Diel’sAlder reaction between cyclopentadiene benzyl acrylate Chiral auxiliary : amide derived from valine via reaction to give asymmetric product 6
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  CHIRAL REAGENTS ANDCHIRAL CATALYSTS  Chiral reagent: enantio specific product  E.g. chiral boron hydride (CBS) Corey, Bakshi, Shibitha 7
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  Enantio selective catalysts enantioselective catalysis are chiral coordination compounds  Ligands show chirality  Privileged ligands :(2,2'-bis(diphenylphosphino)-1,1'- binaphthyl( BINAP),BINOL R- BINAP S- BINAP 8
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  ASYMMETRIC HYDROGENATION 9
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  conclusion  Drug safety Pharmaceuticals  Flavours  Mimic nature 11
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  Reference  Clayden, Jonathan,Nick Greeves and Stuart Warren. Organic Chemistry, 2nd Edition. Oxford. 2012.  Finar, I. L. Organic Chemistry : Stereo Chemistry and Chemistry of Natural Products (vol:2), 5th Edition. Dorling Kindersley Pvt. Ltd. Noida, India. 1975.  Nasipuri, D. Stereochemistry of Organic Compounds: Principles and Applications, 2nd Edition. New Age International Pvt. Ltd. New Delhi. 1994 12
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  Thank you 13