An Efficient Catalytic Stereoselective Route to a Key Intermediate for the Synthesis of the Long-Lived PGI2 Analog ZK 96480 (CicaprostTM)

✍ Scribed by E.J Corey; Christopher J Helal

• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 491 KB
• Volume: 38
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(97)01803-0

✦ Synopsis

An expeditious and stereoselective synthesis ofa key chiral intermediate (2) for the synthesis of the therapeutically usejid PG12analog Cicaprost~is described. @ 1997 ElsevierScienceLtd. Primary pulmonary hypertension (PPH) is an increasingly common and fatal disease. The only lifesustaining treatments for PPH at present are either 24-hour infusion therapy with prostaglandin 12 (PGIz) or combined heart-lung transplant.1 Long lived, metabolically stable, and orally active PGIz analogs such as Cicaprost~(1)2 (dose 0.5 mgjkg, tl/2 ca. 1 h), offer the prospect of a far more acceptable dosing regimen for the first option.3,4 Unfortunately, published syntheses of Cicaprost are long and possibly impractical.s Described herein is a simple and efficient synthetic route to the key intermediate 2 which corresponds to the omega-sidechain of Cicaprost.