Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

Kõllo, Marek; Kasari, Marje; Kasari, Villu; Pehk, Tõnis; Järving, Ivar; Lopp, Margus; Jõers, Arvi; Kanger, Tõnis

doi:10.3762/bjoc.17.52

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…Starting material 2 was recovered in 36% yield (72 mg). The spectral data matched those found in literature [3][4][5][6][7][8][9]27,35,36].…”

Section: Asymmetric Oxidation -Standard Proceduressupporting

confidence: 87%

“…The asymmetric oxidation of sulfide 2 was performed with Ti(iPrO) 4 /(+)-DET/TBHP in a ratio of 1:4:2 by using the known procedure [8]. The obtained results are presented in Table 1.…”

Section: Synthesis Of Enantioenriched 2-(s)-[(4-methylphenyl) Sulfiny...mentioning

confidence: 99%

“…Since the discovery of highly bioactive 9,11-secosterols [1][2][3], our research group has been involved in the elaboration of the chemical access to that family of compounds [4][5][6][7][8]. In eighties of the last century Posner et al demonstrated that substituted cyclopentenone sulfoxides can be used as Michael acceptors for 1-tetralone enolates [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one, a D-ring precursor of 9,11-secosterols

Kõllo¹,

Rõuk²,

Lopp³

2022

PEAS

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The asymmetric oxidation of a key intermediate for 9,11-secosterol synthesis, 2-[(4-methylphenyl)thio]-2-cyclopenten-1one 2 with a Ti(iPrO) 4 /(+)-DET/TBHP complex was studied. The kinetic resolution of racemic 2-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one 1 by oxidation with the same Ti-complex was also carried out. In both cases enantioenriched 2-(S)-[(4methylphenyl)sulfinyl]-2-cyclopenten-1-one 1 was obtained in satisfactory yields and sufficient enantiomeric purity for further enantioenrichment by recrystallization. The obtained results afford simple access to the D-ring precursor of 9,11-secosterols.

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“…Starting material 2 was recovered in 36% yield (72 mg). The spectral data matched those found in literature [3][4][5][6][7][8][9]27,35,36].…”

Section: Asymmetric Oxidation -Standard Proceduressupporting

confidence: 87%

“…The asymmetric oxidation of sulfide 2 was performed with Ti(iPrO) 4 /(+)-DET/TBHP in a ratio of 1:4:2 by using the known procedure [8]. The obtained results are presented in Table 1.…”

Section: Synthesis Of Enantioenriched 2-(s)-[(4-methylphenyl) Sulfiny...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one, a D-ring precursor of 9,11-secosterols

Kõllo¹,

Rõuk²,

Lopp³

2022

PEAS

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“…Thus, KshA3 is largely responsible for the initial specific 9α‐hydroxylation for the formation of 4 . To explore its specificity, substrate 5 was docked into the structural model of KshA3 generated by AlphaFold2 [19,20] . The analysis revealed that 5 was located within a hydrogen bond network consisting of residues I166, Y226 and N251, as well as a water molecule (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

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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“…9,11‐secosterols with unique broken tetracyclic carbon skeletons showcase a wide range of biological properties, encompassing antihistaminic, antiproliferative, anti‐inflammatory and protein kinase C(PKC) inhibition activities [13a–c] . A recent study conducted by Marek Kõllo and colleagues [13d] established a new route for chemoenzymatic synthesis of 9,11‐secosterols. This innovative approach involves using hydrocortisone ( 6 ), a commercially available compound, as the starting material, 9α‐hydroxylase (KshA5) can efficiently and selectively hydroxylate 11β‐hydrocortisone at C9.…”

Section: P450 Hydroxylase‐mediated Chemoenzymatic Synthesis Of Steroidsmentioning

confidence: 99%

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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Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

Cited by 7 publications

References 32 publications

Synthesis of 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one, a D-ring precursor of 9,11-secosterols

Synthesis of 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one, a D-ring precursor of 9,11-secosterols

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

Chemoenzymatic Synthesis of Steroidal Products: Recent Advances

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