134356-45-9Relevant articles and documents
Highly selective lipase-mediated discrimination of diastereomeric 5,6-epoxysteroids
Cruz Silva, M. Manuel,Riva, Sergio,Sa E Melo, M. Luisa
, p. 1173 - 1179 (2004)
Stereoisomerically pure 3β-hydroxy-5,6-epoxysteroids were obtained by combining selective chemical methods for α- and β-epoxidation of Δ5-unsaturated steroids with enzymatic stereoselective esterification of the 3β-hydroxyl group. 5β,6β-Epoxy-3β- hydroxysteroids were efficiently acylated by Novozym 435 and lipase AK, whereas 5α,6α-epoxy-3β-hydroxysteroids were good substrates for Candida rugosa lipase. Mild enzymatic deacylation of the 3β-acetoxy group in the presence of the epoxy functionality was also accomplished by C. rugosa lipase-mediated hydrolysis.
H-Atom Abstraction vs Addition: Accounting for the Diverse Product Distribution in the Autoxidation of Cholesterol and Its Esters
Zielinski, Zosia A. M.,Pratt, Derek A.
, p. 3037 - 3051 (2019/02/19)
We recently communicated that the free-radical-mediated oxidation (autoxidation) of cholesterol yields a more complex mixture of hydroperoxide products than previously appreciated. In addition to the epimers of the major product, cholesterol 7-hydroperoxide, the epimers of each of the regioisomeric 4- and 6-hydroperoxides are formed as is the 5α-hydroperoxide in the presence of a good H-atom donor. Herein, we complete the story by reporting the products resulting from competing peroxyl radical addition to cholesterol, the stereoisomeric cholesterol-5,6-epoxides, which account for 12% of the oxidation products, as well as electrophilic dehydration products of the cholesterol hydroperoxides, 4-, 6-, and 7-ketocholesterol. Moreover, we interrogate how their distribution - and abundance relative to the H-atom abstraction products - changes in the presence of good H-atom donors, which has serious implications for how these oxysterols are used as biomarkers. The resolution and quantification of all autoxidation products by LC-MS/MS was greatly enabled by the synthesis of a new isotopically labeled cholesterol standard and corresponding selected autoxidation products. The autoxidation of cholesteryl acetate was also investigated as a model for the cholesterol esters which abound in vivo. Although esterification of cholesterol imparts measurable stereoelectronic effects, most importantly reflected in the fact that it autoxidizes at 4 times the rate of unesterified cholesterol, the product distribution is largely similar to that of cholesterol. Deuteration of the allylic positions in cholesterol suppresses autoxidation by H-atom transfer (HAT) in favor of addition, such that the epoxides are the major products. The corresponding kinetic isotope effect (kH/kD ～ 20) indicates that tunneling underlies the preference for the HAT pathway.
Solvent-free synthesis of 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol as potential antiproliferative agents
Soto-Castro, Delia,Lara Contreras, Roberto Carlos,Pina-Canseco, María,Santillán, Rosa,Hernández-Huerta, María Teresa,Negrón Silva, Guillermo E.,Pérez-Campos, Eduardo,Rincón, Susana
supporting information, p. 92 - 100 (2017/09/19)
In this paper is described a synthetic route to 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol, starting from cholesterol and diosgenin, respectively. The products were obtained in two steps by epoxidation followed by aminolysis, through an environmentally friendly and solvent-free method mediated by SZ (sulfated zirconia) as catalyst. The use of SZ allows chemo- and regioselective ring opening of the 5,6α-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by 1H, PENDANT 13C NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the β-aminoalcohols was evaluated on MCF-7 cells after 48 h of incubation, by MTT and CVS assays. These methodologies showed that both compounds have antiproliferative activity, being more active the cholesterol analogue. Additionally, the cell images obtained by Harris’ Hematoxylin and Eosin (H&E) staining protocol, evidenced formation of apoptotic bodies due to the presence of the obtained β-aminoalcohols in a dose-dependent manner.
