Structural revisions of the reported A-ring phosphine oxide synthon for ED-71 (Eldecalcitol) and a new synthesis

Abstract

In a reported procedure for the synthesis of the ED-71 A-ring phosphine oxide, we discovered that unusual TBS transfer occurred from the 1α-position to the sterically more constrained 2β-position, and the subsequent Michael addition of ethyl acrylate predominated at the 1α-position. The X-ray analysis of a key intermediate confirmed our observations. We made a structural revision of the reported A-ring phosphine oxide synthon and ED-71. In addition, we provided the first stereoselective synthetic approach to ED-71 A-ring phosphine oxide applying the stereochemistry of d-mannitol.