Towards the total synthesis of amphidinolide T family

QD Chemistry;Q Science (General)

Labre, Flavien ; Clark, Stephen James

University:University of Glasgow

Department:School of Chemistry

关键词: total synthesis, sigmatropic rearrangement, metathesis, amphidinolide, natural product;   

Others  :  http://theses.gla.ac.uk/3642/1/2012LabrePhD.pdf

来源: University of Glasgow

【 摘 要 】

Amphidinolides T are challenging natural targets for the total synthesis community because of their unique structural architecture. This thesis describes the investigations of the establishment of a novel and convenient route to synthesise four members of the natural product family, amphidinolides T1 and T3-5, from a common late-stage intermediate.The key transformations towards the synthetic pathway are ring formation reactions. The trans-tetrahydrofuran ring is forged efficiently via diastereoselective [2,3]-sigmatropic rearrangement of an oxonium ylide from diazo-generated metal carbenoids. Coupling of a side chain is achieved using a sequence of esterification and RCM reactions. Alternatively, a one-pot RCM followed by hydrogenation is described to shorten the synthetic route.