title: Complementary and synergistic roles in enzyme-catalyzed regioselective and complete hydrolytic deprotection of O-acetylated β-D-glucopyranosides of N-arylacetohydroxamic acids.
abstract: An efficient chemoenzymatic synthesis of β-D-glucopyranosides of N-arylacetohydroxamic acids 3a-c was achieved by the chemoselective O-deacetylation of 1a-c under mild, neutral conditions, with no accompanying N-deacetylation. Lipase AS Amano from Aspergillus niger (LAS) and carboxylesterase from Streptomyces rochei (CSR) played complementary, synergistic roles in the O-deacetylation of 1a and its partially O-deacetylated intermediates. An intramolecular O-acetyl migration, which proceeded simultaneously, also accelerated the overall reaction rate. Under weakly acidic conditions at pH 5.0, where the intramolecular O-acetyl migration is markedly slower, LAS, CSR, and porcine liver esterase (PLE) exhibited different regioselective O-deacetylation activities. LAS and PLE showed regioselective 3-O-deacetylation and 2-O-deacetylation activity, respectively, for 1a and its tri-O-acetyl derivatives (4-7). CSR showed marked preferences for 3-O-deacetylation of 2,3,6-tri-O-acetyl intermediate 5 and 4-O-deacetylation of 2,4,6-tri-O-acetyl intermediate 6. In contrast, CSR showed almost no O-deacetylation activity toward the other tri-O-acetyl intermediates 4 and 7, which were efficiently O-deacetylated by LAS in a complementary manner. Using these enzyme-catalyzed regioselective O-deacetylation as well as chemical methods, we could synthesize all 14 partially O-acetylated intermediates (4-17) derived from 1a.
authors.affiliation: Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Baba
authors.forename: Tadao
authors.initials: T
authors.lastname: Yoshioka
mesh_terms: D000107:Acetylation; D001234:Aspergillus niger / Q000201:enzymology; D055162:Biocatalysis; D043182:Carboxylesterase / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005960:Glucosides / Q000138:chemical synthesis*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006877:Hydroxamic Acids / Q000138:chemical synthesis*; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D005960:Glucosides; D006877:Hydroxamic Acids; D043182:Carboxylesterase; D008049:Lipase