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Enantioselective Total Synthesis of (+)‐Plumisclerin A
Author(s) -
Gao Ming,
Wang YeCheng,
Yang KaiRui,
He Wei,
Yang XiaoLiang,
Yao ZhuJun
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201808517
Subject(s) - enantioselective synthesis , total synthesis , moiety , stereocenter , cyclopentane , chemistry , stereochemistry , carbonylation , ring (chemistry) , epoxide , steric effects , conjugate , catalysis , combinatorial chemistry , organic chemistry , carbon monoxide , mathematical analysis , mathematics
The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.0 1,5 ]decane and trans ‐fused dihyrdopyran moiety. Scalable enantioselective La III ‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI 2 ‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans ‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.