Flow Chemistry-Enabled Asymmetric Synthesis of Cyproterone Acetate: A Chemo-biocatalytic Approach DOI Creative Commons
Fen‐Er Chen, Yajiao Zhang, Minjie Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Abstract Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms environmental compatibility, safety and synthetic efficiency especially when scale-up is considered. However, its application manufacturing active pharmaceutical ingredients (APIs) still rare due to the complexity involved with operating a multistep continuous reaction sequence. As demonstration an alternative approach steroid chemistry, herein, we report first 10-step chemo-biocatalytic flow asymmetric cyproterone acetate (4) which 10 transformations are combined into telescoped linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow features engineered 3-ketosteroid-Δ1-dehydrogenase (ReM2)-catalyzed Δ1-dehydrogenation form C1, C2-double bond A ring, substrate-controlled Co-catalyzed Mukaiyama hydration Δ1, 4, 16-triene-3, 20-dione 9 forge crucial chiral C17α-OH group D ring excellent stereoselectivity, rapid Corey-Chaykovsky cyclopropanation 17α-hydroxy-Δ1, 6-triene-3-one-20-ketal 7 build cyclopropyl core ring. By strategic use these three key reactions fully continuous-flow operations, was produced overall yield 9.65% 3 h total time, this shortest route steroid, highest number chemical transformation performance any other reported date. Also included Ni-catalyzed batch-mode nucleophilic using DCM as methylene source for formation disubstituted three-membered on steroids chemo-regio-diastereoselectivity.

Language: Английский

Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach DOI Creative Commons
Yajiao Zhang, Minjie Liu,

Xianjing Zheng

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 27, 2025

Language: Английский

Citations

0
Manganese-Catalyzed Mukaiyama Hydration Reaction for Undergraduate Organic Chemistry Course DOI
Nan Li, Jingyi Zhang, Beibei Ren

et al.

Journal of Chemical Education, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

Citations

0
Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning DOI
Xinqi Xu,

Jinchang Zhong,

Bingmei Su

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 275, P. 133229 - 133229

Published: June 17, 2024

Language: Английский

Citations

1
Manganese/Enzyme Sequential Catalytic Pathway for the Production of Optically Active γ-Functionalized Alcohols DOI
Meng Deng, Jiaqi Yang, Z.-G. Kong

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(12), P. 9103 - 9109

Published: June 6, 2024

A brief, practical catalytic process for the production of optically active γ-functionalized alcohols from relevant alkenes has been developed by using a robust Mn(III)/air/(Me2SiH)2O system combined with lipase-catalyzed kinetic resolution. This approach demonstrates exceptional tolerance toward proximal functional groups present on alkenes, enabling achievement high yields and exclusive enantioselectivity. Under this sequential system, chiral alkene precursors can also be converted into related acetates as separable single enantiomers.

Language: Английский

Citations

1
Improving the bioconversion of phytosterols to 9α-hydroxy-4-androstene-3,17-dione by disruption of acyltransferase SucT and TmaT associated with the mycobacterial cell wall synthesis DOI
Xinxin Chen, Bo Zhang,

Xiaohan Jiang

et al.

World Journal of Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 40(11)

Published: Oct. 15, 2024

Language: Английский

Citations

0
Flow Chemistry-Enabled Asymmetric Synthesis of Cyproterone Acetate: A Chemo-biocatalytic Approach DOI Creative Commons
Fen‐Er Chen, Yajiao Zhang, Minjie Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Abstract Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms environmental compatibility, safety and synthetic efficiency especially when scale-up is considered. However, its application manufacturing active pharmaceutical ingredients (APIs) still rare due to the complexity involved with operating a multistep continuous reaction sequence. As demonstration an alternative approach steroid chemistry, herein, we report first 10-step chemo-biocatalytic flow asymmetric cyproterone acetate (4) which 10 transformations are combined into telescoped linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow features engineered 3-ketosteroid-Δ1-dehydrogenase (ReM2)-catalyzed Δ1-dehydrogenation form C1, C2-double bond A ring, substrate-controlled Co-catalyzed Mukaiyama hydration Δ1, 4, 16-triene-3, 20-dione 9 forge crucial chiral C17α-OH group D ring excellent stereoselectivity, rapid Corey-Chaykovsky cyclopropanation 17α-hydroxy-Δ1, 6-triene-3-one-20-ketal 7 build cyclopropyl core ring. By strategic use these three key reactions fully continuous-flow operations, was produced overall yield 9.65% 3 h total time, this shortest route steroid, highest number chemical transformation performance any other reported date. Also included Ni-catalyzed batch-mode nucleophilic using DCM as methylene source for formation disubstituted three-membered on steroids chemo-regio-diastereoselectivity.

Language: Английский

Citations

0