BIOCATALYTIC SYNTHESIS OF SOME CHIRAL DRUG INTERMEDIATES BY OXIDOREDUCTASES

Chiral intermediates were prepared by biocatalytic processes with oxid oreductases for the chemical synthesis of some pharmaceutical drug can didates. These include: (i) the microbial reduction of (5-fluoro-2-pyr imidinyl)-1-piperazinyl]-1-butanone (1) to -(5-fluoro-2-pyrimidinyl)-1 -piperazinyl]-1-butanol (2) [R-(+)-BMY 14802], an antipsychotic agent; (ii) the reduction of N-4-(1-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide (3) to the corresponding chiral alcohol (4), an intermedi ate for N-4-(1-hydroxy-2-[(-methylethyl)amino]ethyl)phenyl methanesulf onamide [D-(+) sotalol], a beta-blocker with class III antiarrhythmic properties; (i) biotransformation of N epsilon-carbobenzoxy (CBZ)-L-ly sine (7) to N epsilon-CBZ-L-oxylysine (5), an intermediate needed for synthesis of (S)-1-[6-amino-2-{[hydroxy(4-phenyl butyl)phosphinyl]oxy} 1-oxohexyl]-L-proline (ceronapril), a new angiotensin converting enzym e inhibitor (6) and (iv) enzymatic synthesis of L-beta-hydroxyvaline ( 9) from alpha-keto-beta-hydroxyisovalerate (16). L-beta-Hydroxyvaline (9) is a key chiral intermediate needed for the synthesis of -azetidin yl]amino}-2-oxoethylidene]amino}oxyacetic acid (tigemonam) (10), an or ally active monobactam.