Synthesis and biological evaluation of bryostatin analogues: the role of the A-ring

The first biologically active member and a key intermediate of a new family of simplified bryostatin analogues are synthesized through an optimized es terification-macrotransacetalization strategy. This family incorporates bot h an ester linkage between C5 and C9 in addition to a C9 t-butyl substituen t to mimic the bryostatin A-ring. Importantly, a free C7 alcohol is reveale d late in the synthesis, allowing access to numerous C7 derivatized analogu es. (C) 2000 Elsevier Science Ltd. All rights reserved.