Chemoenzymatic synthesis of C14-functionalized steroids

Song, Fuzhen; Zheng, Mengmeng; Wang, Junlin; Liu, Huanhuan; Lin, Zhiang; Liu, Benben; Deng, Zixin; Cong, Hengjiang; Zhou, Qianghui; Qu, Xudong

doi:10.1038/s44160-023-00280-z

Cited by 26 publications

(16 citation statements)

References 64 publications

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“…variable C17 side chains were obtained and then transformed into corresponding ~14 olefins in good-to-excellent yields. [19] Based on the synthetic versatility of the olefin moiety, a diverse of C14-functionalized steroids (for example, β-OH, F, Cl, N 3 , SePh, alkyl, NCO, epoxide, and cyclopropane) were synthesized. Furthermore, with the powerful chemoenzymatic methodology, the concise semisynthesis of cardenolide steroid periplogenin (19) as well as (+)-digitoxigenin (20) and its three diastereomers (21 a-21 c) were achieved (Scheme 4B).…”

Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

“…[19] Based on the synthetic versatility of the olefin moiety, a diverse of C14-functionalized steroids (for example, β-OH, F, Cl, N 3 , SePh, alkyl, NCO, epoxide, and cyclopropane) were synthesized. Furthermore, with the powerful chemoenzymatic methodology, the concise semisynthesis of cardenolide steroid periplogenin (19) as well as (+)-digitoxigenin (20) and its three diastereomers (21 a-21 c) were achieved (Scheme 4B). In the meantime, the chemoenzymatic synthesis of C14β-hydroxyl steroids was also documented by Ge et al In their research, the fungus Curvularia lunata CGMCC 3.9012 was employed as the most suitable strain to introduce the C14α-OH of C17-unsubstituted 4-AD ( 22) with a yield of 70 %.…”

Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

“…To synthesize bufotalin (20), bufogenin B (21) and digitoxigenin (22), a distinct chemosynthesis method was employed to incorporate the C17 substituent (Scheme 4D). [19] The synthesis of C14-functionalized and C19-functionalized steroids is a challenging task for the inert reactivity of C14À H bonds. The aforementioned studies lay the groundwork for the efficient production of a diverse range of C14-functionalized and C19-functionalized steroids, as well as for future investigations aimed at expanding the range of substrates that can undergo enzymatic reactions.…”

Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

See 2 more Smart Citations

Chemoenzymatic Synthesis of Steroidal Products: Recent Advances

Zheng,

Lin,

Lin

et al. 2024

Eur J Org Chem

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The synthesis of steroidal products has garnered sustained interest due to their versatile bioactivities and physicochemical properties in pharmaceutics. However, the complicated structure of steroids, especially their highly oxygenated skeleton, has presented significant challenges. Benefitted from recent advancements in bioinformatics, genetics, and enzyme engineering, chemoenzymatic strategy combines the flexibility of chemical synthesis with the high regio‐ and stereo‐selectivity of biocatalysis, being an effective approach for the concise synthesis of natural products. In this concept, we review and discuss the recent advances in chemoenzymatic approaches for efficient synthesis of steroids and their analogs, as well as future research opportunities and challenges.

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Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

Section: P450 Hydroxylase-mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

See 1 more Smart Citation

Chemoenzymatic Synthesis of Steroidal Products: Recent Advances

Zheng,

Lin,

Lin

et al. 2024

Eur J Org Chem

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“…Quantitative analysis of active CYPs in the membrane is quite challenging, not to mention obtaining their crystal structures. Without the guidance of precise structure, engineering targets for increasing catalytic activity and substrate specificity were confined mostly to amino acids in the substrate recognition sites. , …”

Section: Introductionmentioning

confidence: 99%

“…Without the guidance of precise structure, engineering targets for increasing catalytic activity and substrate specificity were confined mostly to amino acids in the substrate recognition sites. 10,11…”

Section: Introductionmentioning

confidence: 99%

Rational Engineering of a Membrane-Anchored Promiscuous Cytochrome P450 for the Efficient Biosynthesis of Valuable Ganoderic Acids

Luo,

Du,

Jiang

et al. 2023

ACS Catal.

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Biocatalytic Steroidal 9α‐Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10‐Secosteroids

Song,

Zhang,

Cao

et al. 2024

Angewandte Chemie

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9,10‐Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10‐secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase‐like 3‐ketosteroid 9α‐hydroxylase (KSH) as the biocatalyst to achieve efficient C9–C10 bond cleavage and A‐ring aromatization of tetracyclic steroids through 9α‐hydroxylation and fragmentation. With synthesized 9,10‐secosteroides, structure‐activity relationship was evaluated based on bioassays in terms of previously unexplored anti‐infective activity. This study provides experimental evidence to support the hypothesis that the biosynthetic pathway through which 9,10‐secosteroids are formed in nature shares a similar reaction cascade. In addition to the development of a biomimetic approach for 9,10‐secosteroid synthesis, this study highlights the great potential of chemoenzymatic strategies in chemical synthesis.

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Chemoenzymatic synthesis of C14-functionalized steroids

Cited by 26 publications

References 64 publications

Chemoenzymatic Synthesis of Steroidal Products: Recent Advances

Chemoenzymatic Synthesis of Steroidal Products: Recent Advances

Rational Engineering of a Membrane-Anchored Promiscuous Cytochrome P450 for the Efficient Biosynthesis of Valuable Ganoderic Acids

Biocatalytic Steroidal 9α‐Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10‐Secosteroids

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