Asymmetric Total Synthesis of Clinprost

  • Author: ChemistryViews.org
  • Published: 06 December 2020
  • Copyright: Wiley-VCH GmbH
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: Asymmetric Total Synthesis of Clinprost

Prostacyclin, or epoprostenol, is a drug used to treat certain types of hypertension and to inhibit the formation of blood clots. However, it has a very short half-life in the body, and more stable analogues have been synthesized to improve this property. Examples of such analogues are carbacyclin and clinprost (pictured), the methyl ester of isocarbacyclin. The central chiral bicyclo[3.3.0]octene structure of clinprost and similar compounds is a challenging target for organic synthesis. An efficient process for the asymmetric synthesis of clinprost would be useful.


Nariyoshi Umekubo and Yujiro Hayashi, Tohoku University, Sendai, Japan, have developed a pot-economical, asymmetric total synthesis of clinprost. The team started from ethyl 4-oxo-2-pentenoate and 3-(triphenylsilyl)propenal and used an asymmetric domino Michael/Michael reaction catalyzed by a diphenylprolinol silyl ether to obtain the first five-membered ring in a one-pot sequence. Another multi-step one-pot reaction sequence was then used to create a ketone intermediate, which reacted in an intramolecular Horner–Wadsworth–Emmons reaction to give the bicyclo[3.3.0]octenone core. A Suzuki–Miyaura coupling reaction and a second Horner–Wadsworth–Emmons reaction were used to install the side chains.


Clinprost was obtained via seven pots in 17 % total yield and with excellent enantioselectivity. The use of several sequential one-pot transformations makes the synthesis particularly efficient, minimizes waste, and saves time.


 

 

Article Views: 2683

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission and consult our permission guidance prior to making your request

Follow on Facebook Follow on Twitter Follow on YouTube Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH