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Synthesis of the Bicyclic Core of Pumiliotoxins
Author(s) -
Sudau Alexander,
Münch Winfried,
Bats JanW.,
Nubbemeyer Udo
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200210)2002:19<3304::aid-ejoc3304>3.0.co;2-a
Subject(s) - bicyclic molecule , stereocenter , chemistry , diastereomer , stereochemistry , chirality (physics) , ring (chemistry) , enantioselective synthesis , claisen rearrangement , organic chemistry , catalysis , chiral symmetry , nambu–jona lasinio model , quantum mechanics , quark , physics
The bicyclic core of the pumiliotoxins was synthesized in nine to eleven steps starting from L ‐(−)‐proline. This chiral pool starting material was initially converted into an optically active 2‐vinylpyrrolidine by standard operations. The first key step allowed the generation of a nine‐membered ring lactam by means of a zwitterionic aza‐Claisen rearrangement. The 1,4 chirality transfer was found to be low, but the double bond of the azoninone was generated with an exclusive trans configuration in a planar‐ S arrangement. The mixture of diastereomers thus obtained was immediately epoxidized; the planar chiral information could be completely used to build up new stereogenic centers. Subsequent ring closure under hydrogenolytic conditions resulted in the formation of the bicyclic core with a bridgehead of defined configuration. The hydroxyl group of that material could be protected as a TBS ether, or alternatively a sequence of a Swern oxidation and subsequent methyl Grignard addition gave the complete bicyclic framework with low C8 diastereoselectivity. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)