Synthesis of [13]-membered macrocyclic stevastelins via a transesterification reaction as the key step: total synthesis of stevastelin C3

Abstract

A new synthesis of stevastelin C3 ( 3 ), a [13]-membered ring component of the stevastelin family, whose structure was recently revised, is reported. Initially, a macrolactonization approach was attempted to generate the [13]-membered macrolactone but this met with failure, so a translactonization reaction was tried to obtain the targeted stevastelin C3 ( 3 ) from the corresponding [15]-membered ring counterpart. Unfortunately, this strategy did not prove successful, and, consequently, we opted to undertake a transesterification reaction from 23 , as a means to accommodate the requisite aminoacid moiety at the correct position, to obtain 24 . From 24 , and through intermediates 25– 28 , the acyclic precursor of the [13]-membered ring macrolactone, compound 30 , was efficiently prepared. By utilizing the synthetic course developed by Chida, we took 30 forward and completed the total synthesis of stevastelin C3 ( 3 ).