Synthesis and conformational investigation of methyl 4a-carba-D-arabinofuranosides.

Abstract

The synthesis of carbasugar analogues of methyl alpha-D-arabinofuranoside and methyl beta-D-arabinofuranoside (3 and 4) is reported. The route developed involves the conversion of D-mannose into a suitably protected diene (13), which is then cyclized via olefin metathesis. The resulting cyclopentene (14) is stereoselectively hydrogenated to provide an intermediate that can be used for the synthesis of both targets. Through the use of NMR spectroscopy, we have probed the ring conformation of 3 and 4, as well as the rotamer populations about the C(4)-C(5) and C(1)-O(1) bonds. These studies have demonstrated that there are differences in ring conformation between these carbasugars and their glycoside parents (1 and 2). However, only minor differences are seen in the rotameric equilibrium about the C(4)-C(5) bond in 3 and 4 relative to 1 and 2. In regard to the C(1)-O(1) bond, NOE data from 3 and 4 suggest that the favored position about this bond is similar to that in the glycosides; that is, the methyl group is anti to C(2). However, confirmation of this preference through measurement of (3)J(C,C) between the methyl group and C(2) or C(4a) was not successful.