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Synthesis 2014; 46(17): 2333-2346
DOI: 10.1055/s-0033-1338648
DOI: 10.1055/s-0033-1338648
paper
Highly Stereoselective Formal Synthesis of Rosuvastatin and Pitavastatin Through Julia–Kocienski Olefination Using the Lactonized Statin Side-Chain Precursor
Further Information
Publication History
Received: 13 March 2014
Accepted after revision: 24 April 2014
Publication Date:
12 June 2014 (online)
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Abstract
An expedient and simple synthetic approach to pitavastatin and rosuvastatin final intermediates is described. The presented approach consists of completely stereoselective Julia–Kocienski olefination step (E/Z up to 300:1) between lactonized statin side-chain precursor and sulfone derivative of the corresponding pyrimidine and quinoline heterocyclic cores. The desired O-TBS protected statin lactones were isolated in 66–71% yield and high >97% purity (HPLC).
Key words
stereoselective synthesis - olefination - heterocycles - sulfones - lactones - aldehydes - drugsSupporting Information
- for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000084.
- Supporting Information
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Also known as mevinolin, with a brand name of Mevacor® (Merck & Co). For selected literature, see:
For reviews on synthesis of pitavastatin, see:
For the non-Wittig and non-HWE synthesis of pitavastatin, see:
For reviews on Julia–Kocienski olefination, see:
For representative papers and mechanistic discussions on Julia–Kocienski olefination, see:
For patent literature related to the synthesis of statins via Julia–Kocienski olefination with aldehyde type dually protected open side-chain derivatives D, see: