REGIOSELECTIVE PROTECTION STRATEGIES FOR D-XYLOPYRANOSIDES

The acylation of D-xylopyranosides can be effected at any position by selective hydroxyl activation with dibutyltin oxide in refluxing benzene and proper choice of starting anomer. Methyl 4-O-benzyl-beta-D-xylopyranoside, available from methyl 2,3-O-isopropylidene-beta-D-xylopyranoside, provides the 2- and 3-benzoates, which are easily separable in 85% combined yield. Methyl and allyl beta-D-xylopyranosides, when treated with 1 equiv of dibutyltin and subsequently with benzoyl chloride (1 equiv), yield their corresponding 4-benzoates (80%). The use of 2 equiv of benzoyl chloride provides the 3,4-dibenzoates in excellent yield (90%). The clean conversion to mono- or dibenzoates, depending on the amount of benzoyl chloride added, suggests that the intermediate stannylene acetals provide different activation levels. A pathway involving acylation of an intermediate dibutylchlorostannyl ether is proposed to explain the observed phenomenon. This sequential selective activation is used to afford protection and differentiation of the 3- and 4-positions with a one-pot synthesis of methyl 4-O-benzoyl-3-O-(chloroacetyl)-beta-D-xylopyranoside. Methyl and benzyl alpha-D-xylopyranosides afford the 2,4-dibenzoates in good yield (> 80%) demonstrating 1,3-activation of a triol system. This protection strategy is used to prepare benzyl O-(2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl)-(1 --> 3)-2,4-di-O-benzoyl-alpha-D-xylopyranoside from D-xylose and L-arabinose. In the final step, the silver triflate catalyzed glycosylation of benzyl 2,4-di-O-benzoyl-alpha-D-xylopyranoside by 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl chloride is accomplished in 91% yield.