570-85-4Relevant academic research and scientific papers
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.
Oxymercuration-demercuration of steroidal olefins: Extension and reinvestigation
Ahmad, M. S.,Ayad, Tariq M.
, p. 763 - 768 (2007/10/02)
Cholesterol (I) on mercuration-demercuration gives 3β-acetoxycholest-5-ene (II), 3β,6β-dihydroxy-5α-cholestane (V), 6β-acetoxy-3β-hydroxycholest-4-ene (VI), 3β,6β-dihydroxycholest-4-ene (VII) and its diacetate (VIII).Under similar reaction conditions, II affords I, VIII, 3β6β-diacetoxy-5α-cholestane (X) and 5ξ-acetoxycholestan-3-one (XI).On demercuration with NaBH4 - NaOH, the adduct from I gives II, V, VII and cholest-4-en-3-one (IX).Under similar conditions, the adduct from II affords I, V, VII and XI.OM - DM of cholest-5-ene (III) and 3β-chlorocholest-5-ene (IV) has been reinvestigated in order to suport our earlier observation in the sense that 3-substituted products are obtained from III.Cholest-5-ene (III) on OM - DM gives I and II, in addition to the products reported earlier.On demercuration with NaBH4-ethylene glycol the adduct from III gives additional products, such as 4β-acetoxycholest-5-en-7-one (XII) and 7-acetoxy-3β-hydroxycholest-4-en-6-one (XIII).The chloroolefin (IV) on OM - DM gives an additional product, 3β-chloro-6β-hydroxy-5α-cholestane (XIV).Interestingly the mercury adduct from IV on demercuration with NaBH4-ethylene glycol affords an additional product, 3β-(2-acetoxyethoxy)cholest-5-ene (XV).The structures of the compounds have been established by elemental analyses, spectral data, chemical transformation and comparison with authentic samples.Mechanisms for the formation of V and VIII from I and that of II and XII from III have been proposed.
Dissolving Metal Reduction of Esters to Alkanes. A Method for the Deoxygenation of Alcohols
Barrett, Anthony G. M.,Godfrey, Christopher R. A.,Hollinshead, David M.,Prokopiou, Panayiotis A.,Barton, Derek H. R.,et al.
, p. 1501 - 1509 (2007/10/02)
Divers carboxylic esters have been reduced with dissolving Group 1A metals.Using lithium in ethylamine, sterically hindered esters (RCO2R') were deoxygenated giving the alkane (R'H) whereas non-hindered esters regenerated the parent alcohol (R'OH).This permitted the selective deoxygenation of diesters.Conversely, potassium-sodium eutectic solubilised with 18-crown-6 in t-butylamine and tetrahydrofuran (THF) efficiently deoxygenated both hindered and non-hindered esters.In the absence of nucleophiles at ambient temperture the principal reaction of carboxylic ester radical anions was deoxygenation.
The Deoxygenation of NN-Dialkylaminothiocarbonyloxyalkanes
Barrett, Anthony G. M.,Prokopiou, Panayiotis A.,Barton, Derek H. R.
, p. 1510 - 1516 (2007/10/02)
The title compounds were converted into alkanes in high yield on reduction with potassium and 18-crown-6 in t-butylamine.Thereby both primary and secondary alcohols were conveniently deoxygenated.
