Synthesis and conformational analysis of substituted 2,6-dioxabicyclo[3.1.1]heptanes: 1,3-anhydro-2,4-di- O-benzyl-6-deoxy-β- d-glucopyranose by 1H-NMR spectroscopy and molecular mechanics calculation

Abstract

A highly selective ring opening reduction of methyl 3- O-allyl-2- O-benzyl-4,6- O-benzylidene-α- d-glucopyranoside provided the 2,4-di- O-benzyl derivative. This was toluenesulfonylated or iodinated and subsequently reduced to give crystalline methyl 3- O-allyl-2,4-di- O-benzyl-6-deoxy-α- d-glucopyranoside in good yield. Acid hydrolysis followed by deallylation and acetylation afforded a 1,3-diacetate which, on treatment with hydrogen chloride in diethyl ether, gave the crystalline key intermediate 3- O-acetyl-2,4-di- O-benzyl-α- d- glucopyranosyl chloride, Ring closure of the chloride with lithium methoxide afforded 1,3-anhydro-2,4-di- O-benzyl-6-deoxy-β- d-glucopyranose ( 15). Vicinal and long-range proton-proton coupling constants suggested that the conformation of the 1,3-anhydro sugar ether is essentially B 2,5 for the pyranose ring and a chair for the 1,3-dioxane ring. Molecular mechanics calculations using program MMP2 were applied to compound 15 and its analogue, 1,3-anhydro-2,4-di- O-benzyl-β- d-rhamnopyranose, and the results were in good agreement with those calculated by a modified Karplus equation and those measured on molecular models.