Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

Fryszkowska, Anna; Peterson, Justine A.; Davies, Nichola L.; Dewar, C; Evans, George; Bycroft, Matthew; Triggs, Neil; Fleming, Toni; Gorantla, Srikanth Sarat Chandra; Hoge, Garrett; Quirmbach, Michael; Timmanna, Upadhya; Poreddy, Srinivas Reddy; Reddy, Dinne Naresh Kumar; Dahanukar, Vilas H.; Holt-Tiffin, Karen E.

doi:10.1021/acs.oprd.6b00215

Cited by 19 publications

(14 citation statements)

References 34 publications

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“…Reaction condition: 0.5 mmol scale, LaI3 2%, o-Q 4%, DCM/MeCN 1:1, 1 ml. Characterization was in consistent with previous literature31 1. H NMR (400 MHz, CDCl3) δ 5.75 (s, 1H), 2.32 (m, 5H), 1.95 (m, 4H), 1.84 (m, 1H), 1.67 (m, 3H), 1.52 (m, 1H), 1.41 (m, 1H), 1.26 (m, 2H), 1.22 (s, 3H), 1.07 (m, 1H), 0.97 (m, 1H), 0.92 (s, 3H).…”

supporting

confidence: 90%

A Bio-Inspired Lanthanum-Ortho Quinone Catalyst for Aerobic Oxidation of Alcohol

Zhang¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Oxidation reactions are fundamental transformations in organic synthesis and chemical industry. With oxygen or air as terminal oxidant, aerobic oxidation catalysis provides the most sustainable and economic oxidation processes. Most aerobic oxidation catalysis employs redox metal as its active center. While nature provides non-redox metal strategy as in pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDH), such an effective chemical version is unknown. Inspired by the recently discovered rare earth metal-dependent enzyme Ln-MDH, here we show that an open-shell semi-quinone anionic radical species in complexing with lanthanum could serve as a very efficient aerobic oxidation catalyst under ambient conditions. In this catalyst, the lanthanum metal serves only as a Lewis acid promoter and the redox process occurs exclusively on the semiquinone ligand. The catalysis is initiated by 1e--reduction of lanthanum-activated ortho-quinone to a semiquinone-lanthanum complex La(SQ-.)2, which undergoes a coupled O-H/C-H dehydrogenation for aerobic oxidation of alcohols with up to 330 h-1 TOF. This study suggests a possible functional mode of semiquinone radicals, widely observed with quinoproteins in Nature. Moreover, this unique reductive activation strategy as well as the resulted radical anion as redox ligand creates a new turning point in the development of efficient aerobic oxidation catalysis.

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supporting

confidence: 90%

A Bio-Inspired Lanthanum-Ortho Quinone Catalyst for Aerobic Oxidation of Alcohol

Zhang¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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“…4-Aminophenyl- d -galactopyranoside, a biologically relevant glycoside, afforded the desired product in 35% yield ( 82c ). Two other kinds of bioactive molecules derived from mestanolone and dehydroepiandrosterone, respectively, members of the anabolic androgenic class of steroids, showed good reactivities to produce the corresponding products in 56% ( 83c ) and 45% ( 84c ) yields. These examples emphasize the synthetic prospect of this metal-free amination strategy in the pharmaceutical field.…”

Section: Results and Discussionmentioning

confidence: 99%

Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical–Radical Cross-Coupling Powered by Visible Light Photocatalysis

et al. 2020

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Transition-metal-catalyzed C–N bond-forming reactions have emerged as fundamental and powerful tools to construct arylamines, a common structure found in drug agents, natural products, and fine chemicals. Reported herein is an alternative access to heteroarylamine via radical–radical cross-coupling pathway, powered by visible light catalysis without any aid of external oxidant and reductant. Only by visible light irradiation of a photocatalyst, such as a metal-free photocatalyst, does the cascade single-electron transfer event for amines and heteroaryl nitriles occur, demonstrated by steady-state and transient spectroscopic studies, resulting in an amine radical cation and aryl radical anion in situ for C–N bond formation. The metal-free and redox economic nature, high efficiency, and site-selectivity of C–N cross-coupling of a range of available amines, hydroxylamines, and hydrazines with heteroaryl nitriles make this protocol promising in both academic and industrial settings.

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“…Advances in synthetic biology and the increasing importance of methods of sustainable chemistry have brought chemoenzymatic approaches for obtaining natural products, or derivatives thereof, with complex structure into focus [1]. Various enzymatic or semisynthetic methods have also been exploited in the synthesis of steroids [2][3][4]. A more challenging synthesis of secosteroids with unique broken tetracyclic carbon skeletons and abeo-steroids with migrated bonds has received attention only recently [5,6].…”

Section: Introductionmentioning

confidence: 99%

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

Kõllo¹,

Kasari²,

Kasari³

et al. 2021

Beilstein J. Org. Chem.

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A method for the synthesis of 9,11-secosteroids starting from the natural corticosteroid cortisol is described. There are two key steps in this approach, combining chemistry and synthetic biology. Stereo- and regioselective hydroxylation at C9 (steroid numbering) is carried out using whole-cell biocatalysis, followed by the chemical cleavage of the C–C bond of the vicinal diol. The two-step method features mild reaction conditions and completely excludes the use of toxic oxidants.

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Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

Cited by 19 publications

References 34 publications

A Bio-Inspired Lanthanum-Ortho Quinone Catalyst for Aerobic Oxidation of Alcohol

A Bio-Inspired Lanthanum-Ortho Quinone Catalyst for Aerobic Oxidation of Alcohol

Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical–Radical Cross-Coupling Powered by Visible Light Photocatalysis

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

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