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Synthesis of Chiral Building Blocks for Use in Drug Discovery

Author(s): Sharon T. Marino | Danuta Stachurska-Buczek | Daniel A. Huggins | Beata M. Krywult | Craig S. Sheehan | Thao Nguyen | Neil Choi | Jack G. Parsons | Peter G. Griffiths | Ian W. James | Andrew M. Bray | Jonathan M. White | Rustum S. Boyce

Journal: Molecules
ISSN 1420-3049

Volume: 9;
Issue: 6;
Start page: 405;
Date: 2004;
Original page

Keywords: chiral drugs | chiral building blocks | chiral metal catalysts | asymmetric hydrogenation | asymmetric epoxidation | DuPHOS | Noyori catalyst | Jacobsen’s catalyst.

In the past decade there has been a significant growth in the sales of pharmaceutical drugs worldwide, but more importantly there has been a dramatic growth in the sales of single enantiomer drugs. The pharmaceutical industry has a rising demand for chiral intermediates and research reagents because of the continuing imperative to improve drug efficacy. This in turn impacts on researchers involved in preclinical discovery work. Besides traditional chiral pool and resolution of racemates as sources of chiral building blocks, many new synthetic methods including a great variety of catalytic reactions have been developed which facilitate the production of complex chiral drug candidates for clinical trials. The most ambitious technique is to synthesise homochiral compounds from non-chiral starting materials using chiral metal catalysts and related chemistry. Examples of the synthesis of chiral building blocks from achiral materials utilizing asymmetric hydrogenation and asymmetric epoxidation are presented.
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