Issue 30, 2021

A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF, fluprostenol, and travoprost guided by biocatalytic retrosynthesis

Abstract

Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone 6a guided by biocatalytic retrosynthesis, in 11–12 steps with 3.8–8.4% overall yields. An unprecedented Baeyer–Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of 6a (99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones 12 (87 : 13 to 99 : 1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper(II)-catalyzed regioselective p-phenylbenzoylation of the secondary alcohol of diol 10 (9.3 : 1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.

Graphical abstract: A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Jūn. 2021
Accepted
01 Jūl. 2021
First published
01 Jūl. 2021
This article is Open Access

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

Chem. Sci., 2021,12, 10362-10370

A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF, fluprostenol, and travoprost guided by biocatalytic retrosynthesis

K. Zhu, M. Jiang, B. Ye, G. Zhang, W. Li, P. Tang, Z. Huang and F. Chen, Chem. Sci., 2021, 12, 10362 DOI: 10.1039/D1SC03237B

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