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Total Synthesis of Belizentrin Methyl Ester: Report on a Likely Conquest
Author(s) -
Anderl Felix,
Größl Sylvester,
Wirtz Conny,
Fürstner Alois
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.201805125
Subject(s) - intramolecular force , chemistry , total synthesis , aminolysis , polyol , stereochemistry , glycosidic bond , ylide , epoxide , organic chemistry , polyurethane , enzyme , catalysis
The assigned structure of the dinoflagellate‐derived toxin belizentrin was prepared by total synthesis in form of the corresponding methyl ester for stability reasons. The successful route features an unusual solution for the preparation of a recalcitrant ylide on a C‐glycosidic segment; moreover, it involves an asymmetric hetero‐Diels–Alder reaction en route to the tertiary hemiacetal substructure, a Negishi cross‐coupling of two elaborate building blocks, and a macrocyclization based on an intramolecular aminolysis of a spirolactone. A modified Kocienski olefination ultimately allowed the polyol side chain to be attached to the macrocycle although this transformation faced the exceptional base sensitivity of this polyunsaturated target compound.