1164-95-0Relevant academic research and scientific papers
Regioselective esterification of polyhydroxylated steroids by Candida antarctica lipase B
Bertinotti, Anna,Carrea, Giacomo,Ottolina, Gianluca,Riva, Sergio
, p. 13165 - 13172 (1994)
The regioselectivity of Candida antarctica lipase B towards the acetylation of polyhydroxylated steroids has been systematically investigated. The enzyme showed a marked preference for the alcoholic moieties on the A ring and: on the steroidal side chain, making it possible the selective acylation at the positions 3 or 21 of polyhydroxy steroids. Acylation with the synthetically useful esters chloroacetate and levulinate was also accomplished, whereas esterification with benzoate and pivaloate was unsuccessful.
Steroid compound 3-site hydroxyl configuration inversion method
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Paragraph 0025; 0028; 0029, (2018/12/14)
The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.
Remote Oxidation of Aliphatic C-H Bonds in Nitrogen-Containing Molecules
Howell, Jennifer M.,Feng, Kaibo,Clark, Joseph R.,Trzepkowski, Louis J.,White, M. Christina
supporting information, p. 14590 - 14593 (2015/12/08)
Nitrogen heterocycles are ubiquitous in natural products and pharmaceuticals. Herein, we disclose a nitrogen complexation strategy that employs a strong Bronsted acid (HBF4) or an azaphilic Lewis acid (BF3) to enable remote, non-directed C(sp3)-H oxidations of tertiary, secondary, and primary amine- and pyridine-containing molecules with tunable iron catalysts. Imides resist oxidation and promote remote functionalization.
A new and concise way to enamides by fluoroalkanosulfonyl fluoride mediated Beckmann rearrangement of α,β-unsaturated ketoximes
Yan, Zhaohua,Xu, Yun,Tian, Weisheng
supporting information, p. 7186 - 7189 (2015/02/02)
The reaction of α,β-unsaturated ketoximes with fluoroalkanosulfonyl fluorides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) underwent the Beckmann rearrangement smoothly to afford the corresponding acid-sensitive enamides in moderate to excellent yields, which provides a new efficient method for the preparation of acid-sensitive enamides.
The iron(II) complex [Fe(CF3SO3)2(mcp)] as a convenient, readily available catalyst for the selective oxidation of methylenic sites in alkanes
Canta, Merce,Font, David,Gomez, Laura,Ribas, Xavi,Costas, Miquel
supporting information, p. 818 - 830 (2014/04/03)
The efficient and selective oxidation of secondary C-H sites of alkanes is achieved by using low catalyst loadings of a non-expensive, readily available iron catalyst [Fe(II)(CF3SO3)2(mcp)], {Fe-mcp, [mcp=N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)cyclohexane-trans-1,2-diamine]}, and hydrogen peroxide (H2O2) as oxidant, via a simple reaction protocol. Natural products are selectively oxidized and isolated in synthetically amenable yields. The easy access to large quantities of the catalyst and the simplicity of the C-H oxidation procedure make this system a particularly convenient tool to carry out alkane C-H oxidation reactions on the preparative scale, and in short reaction times.
A-ring modified steroidal azoles retaining similar potent and slowly reversible CYP17A1 inhibition as abiraterone
Garrido, Mariana,Peng, Hwei-Ming,Yoshimoto, Francis K.,Upadhyay, Sunil K.,Bratoeff, Eugene,Auchus, Richard J.
, p. 1 - 10 (2014/04/03)
Abiraterone acetate is a potent inhibitor of human cytochrome P450c17 (CYP17A1, 17α-hydroxylase/17,20-lyase) and is clinically used in combination with prednisone for the treatment of castration-resistant prostate cancer. Although many studies have documented the potency of abiraterone (Abi) in a variety of in vitro and in vivo systems for several species, the exact potency of Abi for human CYP17A1 enzyme has not yet been determined, and the structural requirements for high-potency steroidal azole inhibitors are not established. We synthesized 4 Abi analogs differing in the A-B ring substitution patterns: 3α-hydroxy-Δ4-Abi (13), 3-keto- Δ4-Abi (11), 3-keto-5α-Abi (6), and 3α-hydroxy- 5α-Abi (5). We measured the spectral binding constants (Ks) using purified and modified human CYP17A1 along with the determination constants (Ki) applying a native human CYP17A1 enzyme in yeast microsomes for these compounds as well as for ketoconazole. For Abi, 3-keto- Δ4-Abi, 3-keto-5α-Abi, and 3α-hydroxy-5α-Abi, the type 2 spectral changes gave the best fit for a quadratic equation, since in these experiments Ks values were 0.1-2.6 nM, much lower than that for ketoconazole and 3α-hydroxy-Δ4-Abi (Ks values were 140 and 1660 nM, respectively). Inhibition experiments showed mixed inhibition patterns with Ki values of 7-80 nM. Abi dissociation from the CYP17A1-Abi complex was incomplete and slow; the t1/2 for dissociation was 1.8 h, with 55% of complex remaining after 5 h. We conclude that Abi and the 3 related steroidal azoles (3-keto-Δ4-Abi, 3-keto-5α-Abi, and 3α-hydroxy-5α-Abi), which also mimic natural substrates, are extraordinarily potent inhibitors of human CYP17A1, whereas the 3α-hydroxy-Δ4-Abi is moderately potent and comparable to ketoconazole.
Exciton chirality method in vibrational circular dichroism
Taniguchi, Tohru,Monde, Kenji
supporting information; scheme or table, p. 3695 - 3698 (2012/04/11)
The interaction of two IR chromophores yields a strong vibrational circular dichroism couplet whose sign reflects the absolute configuration of the molecule. We present a method to determine absolute configuration of a chiral molecule based on this couplet without need of theoretical calculation. Not only can this method analyze various molecules whose absolute configuration is difficult to determine by other spectroscopic methods, but also it can significantly enhance VCD signals.
Microwave induced selective enolization of steroidal ketones and efficient acetylation of sterols in semisolid state
Marwah, Padma,Marwah, Ashok,Lardy, Henry A.
, p. 2273 - 2287 (2007/10/03)
Under microwave irradiation steroidal enones, more specifically, position three carbonyls were efficiently and selectively converted to the corresponding enol acetates in the presence of additional enolizable carbonyl functions at other positions, using acetic anhydride and a catalytic amount of toluene-p-sulfonic acid. Acetylation of hydroxyl groups of the sterols, including those at the hindered positions, was near quantitative. Strictly anhydrous conditions were not a pre-requisite for acetylation and the reaction system easily tolerated up to 10% (v/v) moisture.
Chemoselective construction of novel steroid derivatives.
Troisi, Luigino,Florio, Saverio,Granito, Catia
, p. 687 - 693 (2007/10/03)
Alpha-halo-alpha-heteroarylalkyllithiums, generated by deprotonation of the corresponding halides, when added promptly to steroids with C=O or C=NR groups, lead to epoxides and aziridines. The reactions are regio- and stereoselective; in fact, in the presence of more than one C=O group, the oxido or aziridino functions are formed uniquely at the C=O of C-17 (or C-20 depending on its position in the starting molecule), and the C-20(R) stereoisomer is often the only product isolated. Protection of the hydroxyl group present on several considered steroids was required, and it was accomplished through derivatization in acetyl, ether, or lactone.
Mass spectrometry of steroid glucuronide conjugates. II - Electron impact fragmentation of 3-keto-4-en- and 3-keto-5α-steroid-17-O-β glucuronides and 5α-steroid-3α,17β-diol 3- and 17-glucuronides
Thevis, Mario,Opfermann, Georg,Schmickler, Hans,Schnzer, Wilhelm
, p. 998 - 1012 (2007/10/03)
The steroid glucuronide conjugates of 16,16,17-d3-testosterone, epitestosterone, nandrolone (19-nortestosterone), 16,16,17-d3-nortestosterone, methyltestosterone, metenolone, mesterolone, 5α-androstane-3α, 17β-diol, 2,2,3,4,4-d5-5α-androstane-3α,17β-diol, 19-nor-5α-androstane-3α,17β-diol, 2,2,4,4-d4-19-nor-5α-androstane-3α,17β-diol and 1α-methyl-5α-androstane-3α/β,17β-diol were synthesized by means of the Koenigs-Knorr reaction. Selective 3- or 17-O-conjugation of bis-hydroxylated steroids was performed either by glucuronidation of the corresponding steroid ketole and subsequent reduction of the keto group or via a four-step synthesis starting from a mono-hydroxylated steroid including (a) protection of the hydroxy group, (b) reduction of the keto group, (c) conjugation reaction and (d) removal of protecting groups. The mass spectra and fragmentation patterns of all glucuronide conjugates were compared with those of the commercially available testosterone glucuronide and their characterization was performed by gas chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. For mass spectrometry the substances were derivatized to methyl esters followed by trimethylsilylation of hydroxy groups and to pertrimethylsilylated products using labelled and unlabelled trimethylsilylating agents. The resulting electron ionization mass spectra obtained by GC/MS quadrupole and ion trap instruments, full scan and selected reaction monitoring experiments are discussed, common and individual fragment ions are described and their origins are proposed. Copyright
