A biocatalytic hydroxylation-enabled unified approach to C19-hydroxylated steroids.

Abstract:

:Steroidal C19-hydroxylation is pivotal to the synthesis of naturally occurring bioactive C19-OH steroids and 19-norsteroidal pharmaceuticals. However, realizing this transformation is proved to be challenging through either chemical or biological synthesis. Herein, we report a highly efficient method to synthesize 19-OH-cortexolone in 80% efficiency at the multi-gram scale. The obtained C19-OH-cortexolone can be readily transformed to various synthetically useful intermediates including the industrially valuable 19-OH-androstenedione, which can serve as a basis for synthesis of C19-functionalized steroids as well as 19-nor steroidal drugs. Using this biocatalytic C19-hydroxylation method, the unified synthesis of six C19-hydroxylated pregnanes is achieved in just 4 to 9 steps. In addition, the structure of sclerosteroid B is revised on the basis of our synthesis.

journal_name

Nat Commun

journal_title

Nature communications

authors

Wang J,Zhang Y,Liu H,Shang Y,Zhou L,Wei P,Yin WB,Deng Z,Qu X,Zhou Q

doi

10.1038/s41467-019-11344-0

subject

Has Abstract

pub_date

2019-07-29 00:00:00

pages

3378

issue

1

issn

2041-1723

pii

10.1038/s41467-019-11344-0

journal_volume

10

pub_type

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