Microbial synthesis of chiral intermediates for β‐3‐receptor agonists

Abstract

AbstractChiral intermediates were prepared by biocatalytic processes for the chemical synthesis of β‐3‐receptor agonists. These include: (i) the microbial reduction of 4‐benzyloxy‐3‐methanesulfonylamino‐2′‐bromoacetophenone 1 to the corresponding (R)‐alcohol 2 by Spingomonas paucimobilis SC 16113. In the biotransformation process, a reaction yield of >85% and an optical purity of 99.5% were obtained for the desired (R)‐alcohol 2; (ii) the enzymatic resolution of racemic α‐methyl phenylalanine amide, 3, and α‐methyl‐4‐hydroxy‐phenylalanine amide, 5, by amidase from Mycobacterium neoaurum ATCC 25795 to prepare the corresponding (S)‐amino acids 4 and 6. Reaction yields of 49.9 and 49 M% (theoretical maximum yield 50 M%) and optical purities of 99 and 94% were obtained for the desired (S)‐amino acids 4 and 6, respectively; (iii) the asymmetric hydrolysis of methyl‐(4‐methoxyphenyl)‐propanedioic acid, ethyl diester, 7, to the corresponding (S)‐monoester 8 by pig liver esterase. A reaction yield of 96 M% and an optical purity of 96% were obtained for (S)‐monoester 8 when reactions were carried out in a biphasic system containing 10% ethanol at 10°C.