Total synthesis of cruentaren A
Author(s)
Fouche, Marianne
Type
Thesis
Abstract
Cruentaren A, a highly cytotoxic metabolite, which also inhibits F-ATPase, was
synthesized using our recently developed methodology on resorcylic acid lactones
natural products. [Molecular structure diagrams appear here. To view, please open pdf attachment] Alcohol A was prepared on a multigram scale in 13 steps starting from (S)-Roche
ester and using highly stereoselective reactions such as Evans aldol reaction and
asymmetric propargylation. [Molecular structure diagrams appear here. To view, please open pdf attachment] Key fragment B was synthesized in 11 steps from 1,3-propanediol. The
1,2-anti-configuration was installed with a Brown crotylation. Diketo-dioxinone D
was generated from C-acylation between Weinreb amide B and keto-dioxinone C. Ketene generation by thermolysis followed by trapping with alcohol A and
aromatization afforded resorcylate derivative E. [Molecular structure diagrams appear here. To view, please open pdf attachment] Finally after a sequence consisting of the following key steps: ring closing alkyne
metathesis, coupling between amine G and acid H and Lindlar hydrogenation,
cruentaren A was obtained. [Molecular structure diagrams appear here. To view, please open pdf attachment]
synthesized using our recently developed methodology on resorcylic acid lactones
natural products. [Molecular structure diagrams appear here. To view, please open pdf attachment] Alcohol A was prepared on a multigram scale in 13 steps starting from (S)-Roche
ester and using highly stereoselective reactions such as Evans aldol reaction and
asymmetric propargylation. [Molecular structure diagrams appear here. To view, please open pdf attachment] Key fragment B was synthesized in 11 steps from 1,3-propanediol. The
1,2-anti-configuration was installed with a Brown crotylation. Diketo-dioxinone D
was generated from C-acylation between Weinreb amide B and keto-dioxinone C. Ketene generation by thermolysis followed by trapping with alcohol A and
aromatization afforded resorcylate derivative E. [Molecular structure diagrams appear here. To view, please open pdf attachment] Finally after a sequence consisting of the following key steps: ring closing alkyne
metathesis, coupling between amine G and acid H and Lindlar hydrogenation,
cruentaren A was obtained. [Molecular structure diagrams appear here. To view, please open pdf attachment]
Date Issued
2011-09
Date Awarded
2012-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Barrett, Anthony
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)