| Abstract
| - An improved and widely applicable chemo-enzymatic method for the synthesis of a series of 1-β-O-acylglucuronides 5a−f has been developed from the corresponding methyl acetyl derivatives 3a−f, whichwere stereospecifically synthesized from cesium salts of carboxylic acids 1a−f and methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-α-d-glucopyranuronate (2). Chemoselectivity of lipase AS Amano (LAS) in thehydrolytic removal of O-acetyl groups of 3a−f to provide methyl esters 4a−f was influenced by thenature of their 1-β-O-acyl groups; high selectivity was evident only for 3b and 3f. Carboxylesterasefrom Streptomyces rochei (CSR), newly screened as an alternative to LAS, showed much greaterchemoselectivity toward the O-acetyl groups than LAS; 3a, 3d, and 3e were chemoselectively hydrolyzedonly by CSR. The combination of CSR with LAS yielded better results in the hydrolysis of 3c and 3fthan did single usage of CSR. Final deprotection of the methyl ester groups of 4a−f to provide 5a−fwas chemoselectively achieved by using lipase from Candida antarctica type B (CAL-B) as well asesterase from porcine liver (PLE), although CAL-B possessed higher chemoselectivity and catalyticefficiency than did PLE. CSR also exhibited high chemoselectivity in the synthesis of (S)-naproxen 1-β-O-acyl glucopyranoside (7) from its 2,3,4,6-tetra-O-acetyl derivative 6.
|
