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Concise Total Synthesis of Enigmazole A
Author(s) -
Ahlers Andreas,
de Haro Teresa,
Gabor Barbara,
Fürstner Alois
Publication year - 2016
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.201510026
Subject(s) - combinatorial chemistry , ring closing metathesis , chemistry , metathesis , stereochemistry , sigmatropic reaction , alkyne , propargyl , catalysis , organic chemistry , polymerization , polymer
Abstract An efficient entry into the phosphorylated marine macrolide enigmazole A is described. Enigmazole A interferes with c‐Kit signaling by an as yet unknown mode of action and is therefore a potential lead in the quest for novel anticancer agents. Key to success is a gold‐catalyzed cascade comprising a [3,3]‐sigmatropic rearrangement of a propargyl acetate along the periphery of a macrocyclic scaffold, followed by a transannular hydroalkoxylation of the resulting transient allenyl acetate. This transformation mandated the use of a chiral gold catalyst to ensure a matching double‐asymmetric setting. Other noteworthy steps are the preparation of the oxazole building block by a palladium‐catalyzed C−H activation, as well as the smooth ring‐closing alkyne metathesis of a diyne substrate bearing a propargylic leaving group, which has only little precedent.