Cyclic Phosphonate Analogs of Hexopyranoses

Acyclic and cyclic analogs of D-glucopyranose and d-mannopyranose have been prepared in which the anomeric carbon has been replaced with a phosphorus. Base-catalyzed addition of dimethyl phosphite to di-O-isopropylidene-d-arabinose followed by recrystallization yields only the acyclic gluco-isomer, through what appears to be a selective recrystallization process. The use of diethyl phosphite under similar conditions yielded only the acyclic manno-isomer. The stereochemistry of each was ascertained through comparison of the pentaacetylated derivatives 11 and 12. For the cyclic analogs 1 and 2, synthesis consists of acid-catalyzed trimethyl phosphite addition to the carbonyl of a hydroxyl-protected open-chain d-arabinose derivative, removal of a formate ester from the 4-hydroxyl group, and base-catalyzed transesterification/cyclization. All four possible cyclic α-hydroxy phosphonate diastereomers were synthesized in roughly equal amounts. Complete separation of the gluco- and manno-isomers was accomplished, and Homonuclear two-dimensional J-spectroscopy was used to supplement standard NMR analysis in order to completely characterize the isolated diastereomers 21 and 22 and assign gluco- and manno-stereochemistry, respectively.