Formal synthesis of the asbestinin family of marine natural products

QD Chemistry

Sigerson, Ralph Clark ; Clark, J. Stephen

University:University of Glasgow

Department:School of Chemistry

关键词: Natural product, total synthesis, marine metabolite;   

Others  :  http://theses.gla.ac.uk/3835/1/2012SigersonPhD.pdf

来源: University of Glasgow

【 摘 要 】

The asbestinins are a sub-class of the ether bridged 2,11-cyclised cembranoid family of marine natural products that have been isolated from octocoral species Briareum Asbestinum. They exhibit high structural complexity and a diverse range of bioactivities that include cytotoxicity against tumour cell lines, potent anti-bacterial properties and antagonism of both histamine and acetylcholine. This report presents the continued efforts in developing an efficient synthetic route to the asbestinins which will be general enough to enable the synthesis of virtually every member of this family of compounds. The key synthetic steps include; a samarium diiodide reductive cyclisation to generate 2,6-syn-5,6-anti tetrahydropyranol motif, oxonium ylide formation with subsequent [2,3]-sigmatropic rearrangement of a functionalised diazoketone and an intramolecular Diels-Alder cycloaddition to construct the cyclohexyl ring.Many studies have been carried out on other sub-classes within the ether bridged 2,11-cyclised cembranoid family of natural products, of particular interest have been the sarcodictyins and cladiellins, the latter of which has been extensively investigated within the Clark group.