Toward the Total Synthesis of Spirastrellolide A.Part 1:Strategic Considerations and Preparation of the Southern Domain

摘要

As part of a program aimed at the discovery of new antimitotic natural products,Andersen and co-workers recently isolated spirastrellolide A (1;Scheme 1) from the Caribbean sponge Spirastrella coccinea.Unlike many other antimitotic macrolides of marine origin,1 does not affect tubulin polymerization in vitro but was shown to be a very potent (IC_(50) = 1 nM) and surprisingly selective inhibitor of protein phosphatase PP2A,with the ability to drive cells directly from the S phase into mitosis before causing cell-cycle arrest.