82206-03-9Relevant academic research and scientific papers
Characterization of chemo- and regioselectivity in enzyme-catalyzed consecutive hydrolytic deprotection of methyl acetyl derivatives of 1-β-O-acyl glucuronides
Baba, Akiko,Yoshioka, Tadao
, p. 74 - 82 (2011/12/22)
Methyl acetyl derivatives of 1-β-O-(o-, m-, or p-phenyl)benzoyl glucuronides 2a-c are fully deprotected by a one-pot consecutive enzyme-catalyzed hydrolytic reaction to afford 4a-c, without isolation of the O-deacetylated derivatives 3a-c. A lipase AS Amano from Aspergillus niger (LAS) and a carboxylesterase from Streptomyces rochei (CSR) showed high chemoselectivity toward the O-deacetylation of the o- and m-isomers, respectively. Chemoselective O-deacetylation of the p-isomer was promoted only in the presence of both enzymes. A lipase type B from Candida antarctica (CALB) was effective for the subsequent enzymatic hydrolysis of the methyl esters of 3a-c. LAS exhibited also regioselective 3-O-deacetylation activity to afford the corresponding 2,4-di-O-acetyl intermediates 5a-c, for which CSR showed higher O-deacetylation activity than that for 2a-c. In kinetic studies using p-nitrophenyl ester substrates, LAS exhibited a broader acyl preference, the octanoyl ester being most effectively hydrolysed, whereas CSR exhibited the highest hydrolytic activity toward the acetyl ester. LAS and CSR play complementary as well as synergistic roles in the O-deacetylation of 2 bearing R groups of different steric bulkiness.
An improved chemo-enzymatic synthesis of 1-β-O-acyl glucuronides: Highly chemoselective enzymatic removal of protecting groups from corresponding methyl acetyl derivatives
Baba, Akiko,Yoshioka, Tadao
, p. 9541 - 9549 (2008/03/27)
(Chemical Equation Presented) An improved and widely applicable chemo-enzymatic method for the synthesis of a series of 1-β-O-acyl glucuronides 5a-f has been developed from the corresponding methyl acetyl derivatives 3a-f, which were 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 the hydrolytic removal of O-acetyl groups of 3a-f to provide methyl esters 4a-f was influenced by the nature of their 1-β-O-acyl groups; high selectivity was evident only for 3b and 3f. Carboxylesterase from Streptomyces rochei (CSR), newly screened as an alternative to LAS, showed much greater chemoselectivity toward the O-acetyl groups than LAS; 3a, 3d, and 3e were chemoselectively hydrolyzed only by CSR. The combination of CSR with LAS yielded better results in the hydrolysis of 3c and 3f than did single usage of CSR. Final deprotection of the methyl ester groups of 4a-f to provide 5a-f was chemoselectively achieved by using lipase from Candida antarctica type B (CAL-B) as well as esterase from porcine liver (PLE), although CAL-B possessed higher chemoselectivity and catalytic efficiency 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.
