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An Expedient Total Synthesis of Chivosazole F: an Actin‐Binding Antimitotic Macrolide from the Myxobacterium Sorangium Cellulosum
Author(s) -
Williams Simon,
Jin Jialu,
Kan S. B. Jennifer,
Li Mungyuen,
Gibson Lisa J.,
Paterson Ian
Publication year - 2017
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.201610636
Subject(s) - stille reaction , stereochemistry , chemistry , total synthesis , alkene , combinatorial chemistry , biochemistry , catalysis
Abstract A unified strategy for the chemical synthesis of the chivosazoles is described. This strategy is based on two closely related approaches involving the late‐stage installation of the isomerization‐prone (2 Z ,4 E ,6 Z ,8 E )‐tetraenoate motif, and an expedient fragment‐assembly procedure. The result is a highly convergent total synthesis of chivosazole F through the orchestration of three mild Pd/Cu‐mediated Stille cross‐coupling reactions, including the use of a one‐pot, site‐selective, three‐component process, in combination with controlled installation of the requisite alkene geometry.