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Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids

Zhao Yang, Qiuyuan Tan, Yan Jiang, Jiaojiao Yang, Xiaojiao Su, Zhen Qiao, Wenqiang Zhou, Ling He, Han‐Yue Qiu, Min Zhang

2021Angewandte Chemie14 citationsDOI

Abstract

Abstract We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L ‐tryptophan as the starting material. Two key bridged skeleton‐forming reactions, namely tandem sequential oxidative cyclopropanol ring‐opening cyclization and ketone α‐allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, N a ‐methyl‐16‐epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N ‐demethylkoumine) with more complex cage scaffolds has been accomplished.

Topics & Concepts

ChemistryTotal synthesisAlleneBiomimetic synthesisStereochemistryKetoneTandemRing (chemistry)Derivative (finance)AlkaloidOrganic chemistryCatalysisEconomicsComposite materialMaterials scienceFinancial economicsAlkaloids: synthesis and pharmacologyTraditional and Medicinal Uses of AnnonaceaeChemical synthesis and alkaloids