Synthesis of Chiral Drug Substances

Abstract

During the last decade the discovery of new drug substances has dramatically changed. New targets derived from genomics, chemical biology, high throughput screening, and combinatorial chemistry have allowed us to speed up the drug discovery process. The changes in the chemical development of identified drug candidates have been less spectacular and have not been the focus of as much public interest. Nevertheless many new synthetic methods, including a great variety of catalytic reactions have been developed and facilitate today the production of complex chiral drug candidates for clinical trials. The present account gives a survey of the syntheses of chiral intermediates and drug substan­ces, that have been performed during the last 10 years within our Chemical Development labs and pilot plant. Particular emphasis is placed on asymmetric hydrogenation, asymmetric epoxidation, asymmetric dihydroxylation and carbon-carbon bond formation, based on chiral metal catalysis.

Key words

asymmetric synthesis - chiral drug substances - metal catalysis (Rh - Ru - Os - V - Ti) - chiral phoshine ligands - chemical and enzymatic resolution - chemical development - pilot plant scale-up

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21

Sharpless AD-Reaction for synthesis of a 2,4,6-Trimethoxy-analogue of ‘Whitesell alcohol’, Jendralla, H. Hoechst AG Frankfurt/M., unpublished results.