☆ 4.8 Article

Concise, scalable and enantioselective total synthesis of prostaglandins

NATURE CHEMISTRY (2021)

Journal

NATURE CHEMISTRY

Volume 13, Issue 7, Pages 692-+

Publisher

NATURE PORTFOLIO

DOI: 10.1038/s41557-021-00706-1

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Categories

Chemistry, Multidisciplinary

Funding

Shenzhen Science and Technology Innovation Committee [KQTD20150717103157174]
Shenzhen Nobel Prize Scientists Laboratory Project [C17783101]
Key-Area Research and Development Program of Guangdong Province [2020B010188001]
Innovative Team of Universities in Guangdong Province [2020KCXTD016]
National Natural Science Foundation of China [21991113, 21901107]
Southern University of Science and Technology (start-up fund)

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Abstract

A practical synthetic strategy for enantioselective and divergent synthesis of prostaglandins was reported, involving the construction of multiply substituted five-membered rings through key enyne cycloisomerization and installation of crucial chiral centers using asymmetric hydrogenation. Common intermediates allowed for the production of various prostaglandins and related drugs in two steps, with the preparation of fluprostenol on a 20-gram scale.

Prostaglandins are among the most important natural isolates owing to their broad range of bioactivities and unique structures. However, current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Here, we report a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of prostaglandins. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key enyne cycloisomerization with excellent selectivity (>20:1 d.r., 98% e.e.). The crucial chiral centre on the scaffold of the prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% e.e.). From our versatile common intermediates, a series of prostaglandins and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale.

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