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Synthesis 2014; 46(17): 2333-2346
DOI: 10.1055/s-0033-1338648
paper
© Georg Thieme Verlag Stuttgart · New York

Highly Stereoselective Formal Synthesis of Rosuvastatin and Pitavastatin Through Julia–Kocienski Olefination Using the Lactonized Statin Side-Chain Precursor

Jan Fabris
a   Cadonic Consultancy Services, LL.C., Cesta na postajo 74, 1351 Brezovica pri Ljubljani, Slovenia
b   Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia
,
Zdenko Časar*
b   Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia
c   Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
d   Sandoz GmbH, Global Portfolio Management API, Biochemiestrasse 10, 6250 Kundl, Austria   Fax: +43(5338)200418   Email: zdenko.casar@sandoz.com
,
Ivana Gazić Smilović
b   Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia
,
Martin Črnugelj
b   Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia
› Author Affiliations
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 - drugs

Supporting 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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