Highly efficient epoxidation of unsaturated steroids using magnesium bis(monoperoxyphthalate) hexahydrate

Carvalho, João F. S.; Silva, M. Manuel Cruz; Melo, M. L. Sá e

doi:10.1016/j.tet.2009.01.100

Cited by 33 publications

(44 citation statements)

References 58 publications

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“…[48] The synthesis of b-epoxy steroids has been achieved by using different chemicalo xidants, such as chromyl diacetate, potassium permanganate salts, chiral ketones combined with oxone,a nd transition metal complexes in the presence of molecular oxygen. [49] Selective biocatalytic oxygen incorporation by UPOs Scheme1.Conversion of testosterone (1)b yCglUPOtot estosterone 4,5b-epoxide (1a)a nd 16a-hydroxytestosterone (1b).…”

Section: Full Papersmentioning

confidence: 99%

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

et al. 2017

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Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less‐activated hydrocarbons, by transferring peroxide‐borne oxygen. We investigated a cell‐free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg−1. Although the well‐known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5‐epoxide of testosterone in β‐configuration and 16α‐hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

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Section: Full Papersmentioning

confidence: 99%

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

et al. 2017

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“…To modulate the steroid ring decoration, epoxidation of the C5=C6 olefin with m CPBA and MMPP was performed, leading to α‐epoxides as major isomers (diastereomeric ratio 4:1 with m CPBA and 85:15 with MMPP). Furthermore, one‐step modification of the secondary alcohol in the A‐ring was performed by means of standard procedures for acetylation, carbonate formation, carbamoylation, and methylation (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling

et al. 2017

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Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone-derived β-lactone as the key intermediate that was transformed into a δ-lactone appended to the D-ring of the steroidal scaffold. This natural-product-inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase-independent manner.

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“…In the presence of cetyl(trimethyl)ammonium hydroxide (CTAOH) at pH 12.5, 2,3-epoxygeraniol (334) is formed exclusively; however, at pH 8.3 in the absence of CTAOH, the formation of 6,7-epoxygeraniol (333) is favored. The magnesium salt of this reagent, magnesium bis(monoperoxyphthalate) hexahydrate (MMPP), is touted as a less expensive and more stable surrogate for mCPBA [382].…”

Section: Using Other Oxidants Without Metal Catalystsmentioning

confidence: 99%

Three‐Membered Heterocycles. Structure and Reactivity

Murphree

2011

Modern Heterocyclic Chemistry

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Highly efficient epoxidation of unsaturated steroids using magnesium bis(monoperoxyphthalate) hexahydrate

Cited by 33 publications

References 58 publications

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling

Three‐Membered Heterocycles. Structure and Reactivity

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