Issue 37, 2023

Organocatalyst-mediated, pot-economical total synthesis of latanoprost

Abstract

The enantioselective total synthesis of latanoprost, an antiglaucoma agent, has been accomplished with excellent diastereo- and enantioselectivities in a pot-economical manner using six reaction vessels. An enantioselective Krische allylation was conducted in the first pot. In the second pot, olefin metathesis, silyl protection, and hydrogenolysis proceeded efficiently. In the third pot, an organocatalyst-mediated Michael reaction proceeded with excellent diastereoselectivity. The fourth pot involved a substrate-controlled Mukaiyama intramolecular aldol reaction and elimination of HNO2 to afford a methylenecyclopentanone, also with excellent diastereoselectivity. The fifth pot involved a Michael reaction of vinyl cuprate. In the sixth pot, three reactions, a cis-selective olefin metathesis, diastereoselective reduction, and deprotection, afforded latanoprost. Nearly optically pure latanoprost was obtained, and the total yield was 24%.

Graphical abstract: Organocatalyst-mediated, pot-economical total synthesis of latanoprost

Supplementary files

Article information

Article type
Edge Article
Submitted
10 jun 2023
Accepted
30 jul 2023
First published
01 aug 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 10081-10086

Organocatalyst-mediated, pot-economical total synthesis of latanoprost

G. Kawauchi, Y. Suga, S. Toda and Y. Hayashi, Chem. Sci., 2023, 14, 10081 DOI: 10.1039/D3SC02978F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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