566-19-8Relevant articles and documents
Microbial transformation of dehydroepiandrosterone (DHEA) by some fungi
Yildirim, Kudret,Kuru, Ali,Y?lmazer Keskin, Semra,Ergin, Sinan
, p. 465 - 474 (2020/11/12)
In this work, biotransformations of dehydroepiandrosterone (DHEA) 1 by Ulocladium chartarum MRC 72584, Cladosporium sphaerospermum MRC 70266 and Cladosporium cladosporioides MRC 70282 have been reported. U. chartarum MRC 72584 mainly hydroxylated 1 at C-7α and C-7β, accompanied by a minor hydroxylation at C-4β, a minor epoxidation from the β-face and a minor oxidation at C-7 subsequent to its hydroxylations. 3β,7β-Dihydroxy-5β,6β-epoxyandrostan-17-one 6, 3β,4β,7α-trihydroxyandrost-5-en-17-one 7 and 3β,4β,7β-trihydroxyandrost-5-en-17-one 8 from this incubation were identified as new metabolites. C. sphaerospermum MRC 70266 converted some of 1 into a 3-keto-4-ene steroid and then hydroxylated at C-6α, C-6β and C-7α, accompanied a minor 5α-reduction and a minor oxidation at C-6 following its hydroxylations. C. sphaerospermum MRC 70266 also hydroxylated some of 1 at C-7α and C-7β. C. cladosporioides MRC 70282 converted almost half of 1 into a 3-keto-4-ene steroid and then hydroxylated at C-6α and C-6β. C. cladosporioides MRC 70282 also reduced some of 1 at C-17.
Metal-Free Allylic Oxidation of Steroids Using TBAI/TBHP Organocatalytic Protocol
Lam, Ying-Pong,Yeung, Ying-Yeung
supporting information, p. 2369 - 2372 (2018/04/19)
A mild, efficient and organocatalytic allylic oxidation of steroids using a TBAI/TBHP protocol has been developed. A range of bioactive Δ5-en-7-ones can be easily prepared from the corresponding Δ5-steroids. The methodology features several advantages, including readily available starting materials, environmentally benign oxidant, high functional group compatibility, and metal-free catalysis.
Scalable and sustainable electrochemical allylic C-H oxidation
Horn, Evan J.,Rosen, Brandon R.,Chen, Yong,Tang, Jiaze,Chen, Ke,Eastgate, Martin D.,Baran, Phil S.
, p. 77 - 81 (2016/06/01)
New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as € classics €. Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.
Biohydroxylation of 7-oxo-DHEA, a natural metabolite of DHEA, resulting in formation of new metabolites of potential pharmaceutical interest
?wizdor, Alina,Panek, Anna,Milecka-Tronina, Natalia
, p. 844 - 849 (2016/11/11)
Metabolism of steroids in healthy and unhealthy human organs is the subject of extensive clinical and biomedical studies. For this kind of investigations, it is essential that the reference samples of new derivatives of natural, physiologically active steroids (especially those difficult to achieve in the chemical synthesis) become available. This study demonstrated for the first time transformation of 7-oxo-DHEA—a natural metabolite of DHEA, using Syncephalastrum racemosum cells. The single-pulse fermentation of substrate produced two new hydroxy metabolites: 1β,3β-dihydroxy-androst-5-en-7,17-dione and 3β,12β-dihydroxy-androst-5-en-7,17-dione, along with the earlier reported 3β,9α-dihydroxy-androst-5-en-7,17-dione and 3β,17β-dihydroxy-androst-5-en-7-one. Simultaneously, the same metabolites, together with small quantities of 7α- and 7β-hydroxy-DHEA, as well as the products of their reduction at the C-17 were obtained after transformation of DHEA under pulse-feeding of the substrate. The observed reactions suggested that this micro-organism contains enzymes exhibiting similar activity to those present in human cells. Thus, the resulting compounds can be considered as potential components of the eukaryotic, including human, metabolome.
N-Hydroxyphthalimide catalyzed allylic oxidation of steroids with t-butyl hydroperoxide
Zhao, Qian,Qian, Chao,Chen, Xin-Zhi
, p. 1 - 6 (2015/02/19)
A new and optimized procedure for the allylic oxidation of Δ5-steroids with t-butyl hydroperoxide in the presence of catalytic amounts of N-hydroxyphthalimide (NHPI) under mild conditions was developed, showing excellent regioselectivity and chemoselectivity (functional group compatibility). It was found that Co(OAc)2 could enhance the catalytic ability of NHPI resulting in better yields and shorter reaction times. The reaction mechanism and the scope of the reaction with a variety of Δ5-steroidal substrates were also investigated.
Allylic oxidation of steroidal olefins by vanadyl acetylacetonate and tert-butyl hydroperoxide
Grainger, Wendell S.,Parish, Edward J.
, p. 103 - 109 (2015/06/30)
Abstract Readily available vanadyl acetylacetonate was found to oxidize the allylic sites of Δ5 steroidal alcohols without protection of hydroxyl groups. Cholesterol, dehydroepiandrosterone, cholesterol benzoate, cholesterol acetate, pregnenolone, and 5-pregnen-3,20-diene were oxidized to 7-keto products using vanadyl acetylacetonate in one pot reactions at room temperature in the presence of oxygen and water.
Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids?
Milecka-Tronina, Natalia,Ko?ek, Teresa,?wizdor, Alina,Panek, Anna
, p. 883 - 891 (2014/01/23)
In this paper we focus on the course of 7-hydroxylation of DHEA, androstenediol, epiandrosterone, and 5α-androstan-3,17-dione by Absidia coerulea AM93. Apart from that, we present a tentative analysis of the hydroxylation of steroids in A. coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition analysis together with (iv) geometrical relationship between the C-H bond of the substrate undergoing hydroxylation and the cofactor-bound activated oxygen atom, it is postulated that the same enzyme can catalyze the oxidation of C7-Hα as well as C7-H β bonds in 5-ene and 5α-dihydro C19-steroids. Correlations observed between the structure of the substrate and the regioselectivity of hydroxylation suggest that 7β-hydroxylation may occur in the normal binding enzyme-substrate complex, while 7α-hydroxylation - in the reverse inverted binding complex.
Hydroxylation of DHEA, androstenediol and epiandrosterone by Mortierella isabellina AM212. Evidence indicating that both constitutive and inducible hydroxylases catalyze 7α- as well as 7β-hydroxylations of 5-ene substrates
Kolek, Teresa,Milecka, Natalia,Swizdor, Alina,Panek, Anna,Bialonska, Agata
, p. 5414 - 5422 (2011/09/13)
The course of transformation of DHEA, androstenediol and epiandrosterone in Mortierella isabellina AM212 culture was investigated. The mentioned substrates underwent effective hydroxylation; 5-ene substrates - DHEA and androstenediol - were transformed into a mixture of 7α- and 7β- allyl alcohols, while epiandrosterone was converted into 7α- (mainly), 11α- and 9α- monohydroxy derivatives. Ketoconazole and cycloheximide inhibition studies suggest the presence of constitutive and substrate-induced hydroxylases in M. isabellina. On the basis of time course analysis of the hydroxylation of DHEA and androstenediol, the oxidation of allyl C7-Hα and C7-Hβ bonds by the same enzyme is a reasonable assumption.
CrO3/NHPI adsorbed on activated clay: A new supported reagent for allylic selective oxidation of Δ5-sterols
Liu, Jin,Zhu, Hong-You,Cheng, Xiao-Hong
experimental part, p. 1076 - 1083 (2009/09/06)
Chromium trioxide and N-hydroxyphthalimide (NHPI) supported on activated clay could serve as an efficient and mild oxidant for allylic selective oxidation of Δ5-sterols. Thus, a ketone group could be easily introduced into the allylic position of Δ5-sterols with the existence of a sensitive 3β-hydroxyl group. The oxidant residue can be removed easily from the reaction mixture by filtration and reused after reactivation at 120δC for 4-6 h. Copyright Taylor & Francis Group, LLC.
Optimal TBHP allylic oxidation of Δ5 - Steroids catalyzed by dirhodium caprolactamate
Choi, Hojae,Doyle, Michael P.
, p. 5349 - 5352 (2008/09/17)
Dirhodium caprolactamate is the most efficient catalyst for the oxidation of Δ5-steroids to 7-keto-Δ5-steroids by 70% tert-butyl hydroperoxide in water (T-HYDRO). Isolated product yields range from 38 to 87%.
