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Synfacts 2014; 10(1): 0006
DOI: 10.1055/s-0033-1340325
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

A Formal Synthesis of Atorvastatin

Contributor(s):
Philip Kocienski
Kobayashi Y, Taniguchi Y, Hayama N, Inokuma T, Takemoto Y * Kyoto University, Japan
A Powerful Hydrogen-Bond-Donating Organocatalyst for the Enantioselective Intramolecular Oxa-Michael Reaction of α,β-Unsaturated Amides and Esters.

Angew. Chem. Int. Ed. 2013;
52: 11114-11118
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Further Information

Publication History

Publication Date:
13 December 2013 (online)

 
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Key words

atorvastatin - enantioselectivity - oxa-Michael reaction - organocatalysis

Significance

The key step in this formal synthesis of atorvastatin (Lipitor®) is the enantioselective intramolecular oxa-Michael reaction of A mediated by 10 mol% of benzothiadiazine catalyst B. Methods for converting G and its relatives into ­atorvastatin have been summarized by Y. Kawato et al. (Chem. Eur. J. 2013, 19, 3802; see also references therein).


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Comment

For the conversion of N-nitrosamides into esters (e.g., D → E), see: D. T. Glatzhofer, R. R. Roy, K. N. Cossey Org. Lett. 2002, 4, 2349. Phenolic nucleophiles (14 examples) also participate in the oxa-Michael reaction, and in the case of H only 1 mol% of catalyst I is required.


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