Evidence for pi-stacking as a source of stereocontrol in the synthesis of the core pyranochromene ring system common to calyxin I, calyxin J, and epicalyxin J.

A diastereoselective synthesis of the tetrahydropyranochromene ring system common to several natural product isolates of Alpinia blepharocalyx is reported. We have shown that a stereochemical preference exists for a syn configuration between the anomeric aryl substituents, representative of the C-7 and C-7' substituents in the natural products. Further, our results show that stereocontrol is under kinetic control, and calculations suggest that a favorable pi-stacking interaction may be the source of this stereocontrol.

Stereoselective approach to C-aryl pyranoside synthesis which addresses the problem of C7-substitution in blepharocalyxin E.

A general route to a series of aryl-substituted pyranoside derivatives has been developed as a model for the synthesis of blepharocalyxin E. Two exo-substituted tetrahydro-4H-furo[2,3-b]pyran-2-one derivatives, 8a and 8b, were prepared and treated separately with anisole and phenoxytriisopropylsilane under Lewis acid conditions to effect C-aryl pyranoside synthesis. In each case, a gamma-lactone was formed, which rearranged to the desired structure on acid treatment. Four compounds (12, 14, 16, and 18) were prepared by this route as single isomers in good overall yield.