Total Synthesis of the Hydroxyketone Kurasoin A Using Asymmetric Phase-Transfer Alkylation

The total synthesis of the farnesyltransferase inhibitor kurasoin A has been achieved using a novel asymmetric phase-transfer-catalyzed glycolate alkylation reaction. 2,5-Dimethoxyacetophenone 7 with cinchonidinium catalyst 9 (10 mol %) and hydroxide base with pivaloyl benzyl bromide 8 provided S-al...

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Bibliographic Details
Published in:Journal of organic chemistry 2006-10, Vol.71 (22), p.8651-8654
Main Authors: Andrus, Merritt B, Hicken, Erik J, Stephens, Jeffrey C, Bedke, D. Karl
Format: Article
Language:English
Subjects:
Alkylation
Catalysis
Catalysts: preparations and properties
Chemistry
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Exact sciences and technology
Farnesyltranstransferase - antagonists & inhibitors
General and physical chemistry
Hydroxylation
Indoles - chemical synthesis
Indoles - chemistry
Ketones - chemistry
Molecular Structure
Organic chemistry
Phenols - chemical synthesis
Phenols - chemistry
Substrate Specificity
Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
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Summary:The total synthesis of the farnesyltransferase inhibitor kurasoin A has been achieved using a novel asymmetric phase-transfer-catalyzed glycolate alkylation reaction. 2,5-Dimethoxyacetophenone 7 with cinchonidinium catalyst 9 (10 mol %) and hydroxide base with pivaloyl benzyl bromide 8 provided S-alkylation product 10 in high yield (80−99%) and excellent enantioselectivity. Baeyer−Villiger oxidation, Weinreb amide formation, and benzyl Grignard addition to the TES-ether 17 gave the protected target. Lithium hydroxide and peroxide generated kurasoin A ([α]D +8.4°) without isomerization.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo061395t