Microbial synthesis of chiral intermediates for b-3-receptor agonists

• Published in: Journal of the American Oil Chemists' Society Vol. 75; no. 11; pp. 1473 - 1482
• Main Authors: Patel, Ramesh N, Banerjee, Amit, Chu, Linda, Brozozowski, David, Nanduri, Venkata, Szarka, Laszlo J
• Format: Journal Article
• Language: English
• Published: 01.11.1998
• Subjects: Mycobacterium neoaurum
• ISSN: 0003-021X; 1558-9331
• DOI: 10.1007/s11746-998-0081-0

Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of b-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 a-methyl phenylalanine amide, 3, and a-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.