文摘
A practical second-generation synthesis of an advanced intermediate in our total synthesis ofaltohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features avinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install thetroublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained,but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalizationreaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g ofintermediate 57 has been produced using this improved route.