Regioselective C‐6 Hydrolysis of MethylO‐Benzoyl‐pyranosides Catalysed byCandida RugosaLipase

Abstract

Hydrolysis of six methyl O‐benzoyl‐pyranosides has been investigated using Candida rugosa lipase in dioxane/buffer mixtures. The lipase catalysed the hydrolysis of all substrates in a regiospecific manner at C‐6. The rate of reaction was dependent on pyranoside structure, reaction temperature and scale, dioxane concentration and agitation speed. Starting from their C‐6 O‐benzoyl precursors, the methyl 2,3,4‐tri‐O‐benzoyl‐pyranosides of α‐D‐galactose, β‐D‐galactose, α‐D‐glucose, and methyl 2,3‐di‐O‐benzoyl‐α‐D‐galactopyranoside could be isolated in 85–96 % yield. In hydrolysis of methyl 2,3,4,6‐tetra‐O‐benzoyl‐α‐D‐glucopyranoside and methyl 2,3,4,6‐tetra‐O‐benzoyl‐β‐D‐galactopyranoside substrate inhibition were observed, which in part could be overcome by increasing the reaction volume. Methyl 2,3,4,6‐tetra‐O‐benzoyl‐β‐D‐glucopyranoside and methyl 2,3,4,6‐tetra‐O‐benzoyl‐α‐D‐mannopyranoside were poor substrates for Candida rugosa lipase and low degree of conversion towards products were obtained under all conditions. No acyl migration was detected in any of the products.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis and Structure Elucidation of Benzoylated Deoxyfluoropyranosides

“…These were obtained by two different routes: compounds 4a-c were synthesized by Candida rugosa lipase (CRL)-catalyzed hydrolysis of the corresponding tetrabenzoates, 2a-c, as previously reported, [27] while 4d-e were obtained by a tritylation/benzoylation/detritylation protocol (Sch. 1).…”

“…69-70 • C, [α] 22 D = −127.5 • (c 0.5, CHCl 3 ), lit. [27] −126.0 • (c 0.5, CHCl 3 ), lit. [38] −154 • (c 1.1, CHCl 3 ).…”

“…1 H NMR (CDCl 3 ) and 13 C NMR (CDCl 3 ) corresponded with data reported previously. [27,38] [41,42] Methyl α-D-mannopyranoside (2.00, 10.30 mmol) was converted to methyl 2,3,4-tri-O-benzoyl-6-trityl-α-D-mannopyranoside (3e) [40,43] as described for 4d. This gave 2.70 g (3.61 mmol, 35%) of 3e as a white solid, mp.…”

“…The compounds 2a-c, 4a-c, and 9a were prepared as described previously. [27,37] Solvents were from VWR and were used as received, except for CH 2 Cl 2 , which was dried over CaCl 2 . Column chromatography was performed using silica gel 60A from Fluka (pore size 40-63 µm).…”

“…Compound 5b was synthesized as described for 5a, starting with 4b (100 mg, 0.20 mmol) giving 9 mg (0.02 mmol, 9%) of a colorless oil; [35] DAST (190 µL, ∼232 mg, ∼1.44 mmol) was added drop-wise to a solution of 4c [27] (180 mg, 0.36 mmol) and DMAP (100 mg, 0.80 mmol) in dry CH 2 Cl 2 (3 mL) at −25 • C. After stirring under argon for 12 h, the reaction mixture was allowed to warm to ambient temperature, stirred overnight, and refluxed for 1 h. The mixture was then cooled to 0 • C and methanol (0.5 mL) was added to quench the reaction. The reaction mixture was then diluted with CH 2 Cl 2 (10 mL) and washed with saturated NaHCO 3 (3 × 10 mL) and water (10 mL), and the aqueous phase was back-extracted once with CH 2 Cl 2 (10 mL).…”