- Investigation on the synthesis of 25-hydroxycholesterol
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A very efficient and environmentally benign method has been developed for the synthesis of 25-hydroxycholesterol. The reaction was performed in THF-water (4:1, v/v) using NBS as the brominating agent, followed by the easy reduction of C-Br with lithium aluminum hydride in THF, to yield the final product corresponding to a Markovnikov's rule. Excellent yields and regioselectivity have been obtained.
- Zhao, Qian,Ji, Li,Qian, Guo-Ping,Liu, Jian-Gang,Wang, Zi-Qiang,Yu, Wan-Feng,Chen, Xin-Zhi
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- Enzymatic Regioselectivity in the Hydroxylation of Cholesterol Catalyzed by a Membrane-Spanning Metalloporphyrin
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The hydroxylation of simple alkanes and the selective C-25 hydroxylation of cholesterol have been achieved with a membrane-spanning Mn(III) porphyrin positioned in a synthetic bilayer assembly by appended steroidal substituents.
- Groves, John T.,Neumann, Ronny
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- A comparison of the potential unfavorable effects of oxycholesterol and oxyphytosterol in mice: Different effects, on cerebral 24S-hydroxychoelsterol and serum triacylglycerols levels
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Sterol oxidation products derived from cholesterol and phytosterol are formed during the processing and storage of foods. The objective of the present study was to assess the potential unfavorable effects of oxysterols in mice. C57BL/6J mice were fed an AIN-93G-based diet containing 0.2 g/kg of oxycholesterol or oxyphytosterol for 4 weeks. The most abundant oxysterol in the diet was 7-ketosterol, but α-epoxycholesterol, β-epoxycholesterol, or 7α-hydroxyphytosterol, and 7β-hydroxyphytosterol were more prominent than 7-ketosterol in the serum and liver respectively. Consumption of both oxysterols resulted in an increased in 4β-hydroxycholesterol and total oxycholesterol in the liver, but the oxycholesterol-fed mice had a lower level of cerebral 24S-hydroxycholesterol and a higher level of the serum triacylglycerols than the control and oxyphytosterol groups. These results indicate that both oxysterols in the diet are accumulated in the body, but that the biological effect of oxycholesterol is different from that of oxyphytosterol.
- Bang, Hyun-Jung,Arakawa, Chiyo,Takada, Michihiro,Sato, Masao,Imaizumi, Katsumi
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- Preparation of oxysterols by c–h oxidation of dibromocholestane with ru(Bpga) catalyst
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Seven mono-and dihydroxycholesterols were prepared by direct C–H oxidation of the cholestane skeleton with a recently developed Ru(Bpga) catalyst (Ru(Bpga) = [RuCl (bpga) (PPh3 )] Cl; bpga = 2-(bis(pyridin-2-ylmethyl)amino)-N-(2,6-dimethylphenyl)acetamide)). Due to the high selectivity of the Ru(Bpga) complex for tertiary C–H, the reaction afforded a mixture of 25-, 20-, 17-, and 14-oxygenated cholesterols that could be easily separated by high-performance liquid chromatography. These results suggest that late-stage C–H oxidation could be a viable strategy for preparing candidate metabolites of biologically important molecules.
- Doiuchi, Daiki,Fujii, Yui,Hirai, Go,Igawa, Kazunobu,Makino, Kana,Takeda, Daiki,Tomooka, Katsuhiko,Uchida, Tatsuya,Yoritate, Makoto
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- Method for synthesizing and purifying 25-hydroxycholesterol
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The invention belongs to the technical field of organic chemical synthesis and relates to a method for synthesizing and purifying 25-hydroxycholesterol. The method comprises the following steps that: (1) a mixture containing a compound as shown in a formula (I) and a compound as shown in a formula (II) contacts with an addition reagent, so that an addition product can be obtained, on the basis of the total weight of the mixture, the content of the compound as shown in the formula (I) is 10-60 wt%, the addition reagent has a structure as shown in a formula (III), in the formula (I) and the formula (II), R1 is H or C1-C4 acyl, in the formula (III), R2 is a C1-C4 acyl, and R1 and R2 are the same or different; (2) saponification reaction is carried out on the addition product and alkali to obtain a saponification product; and crystallization and separation are performed to obtain the 25-hydroxycholesterol. The method for preparing the 25-hydroxycholesterol has the advantages of easy-to-obtain raw materials and simple and safe process steps.
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Paragraph 0091-0093
(2021/07/31)
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- Methods for preparing cholesterol, and derivatives and analogs thereof
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The present invention relates to the field of pharmaceutical chemistry, and in particular to methods of preparing cholesterol,and derivatives and analogs thereof. The cholesterol derivatives include, but not limited to, 7-dehydrocholesterol, 25-hydroxycholesterol, 25- hydroxy7dehydrocholesterol and ergosterol. In the invention, phytosterol can be used as a raw material to prepare the compound shown in the formula I through microbial conversion, and then cholesterol and the derivatives and analogues thereof are prepared.
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- NOVEL METHOD FOR SYNTHESIZING 25-OH CHOLESTEROL/CALCIFEDIOL FROM PHYTOSTEROL
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The present invention discloses novel method for synthesizing vegan 25-OH cholesterol/Calcifediol from inexpensive crude phytosterol. According to the method, Phytosterols are reacted to form corresponding i-steroid through tosylation and methanolysis. i-steroid on reductive ozonolysis to C-22 alcohol and conversion via C-22 tosylate to C-22 iodide in good yield. Coupling of C-22 tosylate with Grignard reagent of 4-bromo-2-methyl-2-[(trimethylsilyl)oxy] butane followed by deprotection yielded 25-OH cholesterol. In a process variant, nickel mediated conjugate addition of C-22 iodide to an electron deficient alkene ethyl acrylate and treating corresponding ester with methyl magnesium bromide as means of installing the side chain of 25-OH cholesterol in high yield. Further bromination reaction of 25-OH cholesterol diacetate followed by dehydrobromination using TBAF yielded 25-OH 7-dehydrocholesterol. Further photo reaction of 25-OH 7-dehydrocholesterol in to previtamin D3 using high or medium pressure mercury lamp and subsequent thermal reaction of previtamin D3 to 25-OH vitamin D3(Calcifediol) in good yield.
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Page/Page column 12; 14; 21-22
(2020/11/23)
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- A concise synthesis of 25-Hydroxycholesterol from hyodesoxycholic Acid
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A simple, efficient and economical method has been developed for the synthesis of 25-hydroxycholesterol in seven steps from hyodesoxycholic acid with an overall yield of 39%. The preparation of the 3β-tetrahydropyranyloxychol-5-en-24-al from 3β-tetrahydropyranyloxychol-5-en-24-oic acid methyl ester with di-isobutylaluminium hydride was achieved instead of using the conventional two-step reaction, thus avoiding the use of the toxic oxidant CrO3. The terminal product was obtained by hydroxybromination of desmosterol with N-bromosuccinimide/H2O, followed by reduction and deprotection of the halohydrins with LiAlH4. This simplified route gave an increased overall yield and used economical and environmentally benign reagents.
- Jin, Can,Wang, Yulei,Sun, Bin,Su, Weike
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- Cyclic cholane carboxylate derivative, preparation method and uses thereof
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The present invention provides a cyclic cholane carboxylate derivative and a preparation method thereof, and uses of the cyclic cholane carboxylate derivative in industrial preparation of 25-hydroxycholesterol (1), wherein R1 in the cyclic cholane carboxylate derivative represented by a formula I is straight chain or branched chain C1-C12 alkyl, R2 is methyl or ethyl, and the formula (I) is defined in the specification. According to the present invention, the starting raw material stigmasterol of the 25-hydroxycholesterol (1) synthesis process route has characteristics of low price, easy obtaining and reliable commercial source; and particularly during the constructing of the 17-position side chain of 25-hydroxycholesterol (1), the reaction conditions are mild, the reaction steps are simple, the special and dangerous reagents are not required, the harsh reaction conditions are not required, the redundant reaction steps are not required, the chromatographic separation and purification is not required, the industrial production is easily achieved, and the significant progress is achieved compared to the prior art.
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- OXYSTEROLS AND METHODS OF USE THEREOF
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Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R2, R3, R4, R5, and and R6 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
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Paragraph 00724; 00725
(2018/05/16)
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- Synthesis of side-chain oxysterols and their enantiomers through cross-metathesis reactions of Δ22 steroids
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A synthetic route that utilizes a cross-metathesis reaction with Δ22 steroids has been developed to prepare sterols with varying C-27 side-chains. Natural sterols containing hydroxyl groups at the 25 and (25R)-26 positions were prepared. Enantiomers of cholesterol and (3β,25R)-26-hydroxycholesterol (27-hydroxycholesterol) trideuterated at C-19 were prepared for future biological studies.
- Brownholland, David P.,Covey, Douglas F.
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- Cholesterol Hydroperoxides as Substrates for Cholesterol-Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25-Hydroxycholesterol and other Oxysterols
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The interaction of the primary autoxidation products of cholesterol, namely 25- and 20ξ-hydroperoxides, with the four principal cholesterol-metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25-hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well-defined spectral changes while generating 25-hydroxycholesterol as the major product. The 20ξ-hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide-shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate. CYP27A1 was shown to mediate the reduction of cholesterol 25-hydroperoxide to 25-hydroxycholesterol, a role of potential significance for cholesterol-rich tissues with high oxidative stress. CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25-hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry.
- van Lier, Johan E.,Mast, Natalia,Pikuleva, Irina A.
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p. 11138 - 11142
(2016/07/06)
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- Cholesterol transformations during heat treatment
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The aim of the study was to characterise products of cholesterol standard changes during thermal processing. Cholesterol was heated at 120 °C, 150 °C, 180 °C and 220 °C from 30 to 180 min. The highest losses of cholesterol content were found during thermal processing at 220 °C, whereas the highest content of cholesterol oxidation products was observed at temperature of 150 °C. The production of volatile compounds was stimulated by the increase of temperature. Treatment of cholesterol at higher temperatures i.e. 180 °C and 220 °C led to the formation of polymers and other products e.g. cholestadienes and fragmented cholesterol molecules. Further studies are required to identify the structure of cholesterol oligomers and to establish volatile compounds, which are markers of cholesterol transformations, mainly oxidation.
- Derewiaka,Molińska
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p. 233 - 240
(2015/01/09)
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- Synthesis of 24-functionalized oxysterols
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The syntheses of (24S)-24,25-epoxycholesterol, (24S)-hydroxycholesterol, and 24-ketocholesterol are described. The compounds belong to oxysterols, which can be considered to be the modulators of cholesterol metabolism. The asymmetric hydroxylation of desmosterol acetate according to Sharpless was used as the key reaction in the stereoselective introduction of functionality in position 24.
- Khripach,Zhabinskii,Konstantinova,Khripach,Antonchick
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p. 257 - 261
(2007/10/03)
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- Selective oxidation of terminal isopropyl groups to tertiary alcohols by electrochemical methodology
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Selective oxidation of terminal isopropyl groups to the corresponding tertiary alcohols by an electrochemical method is described. Under the conditions using the TI(TFA)3-hematoporphyrin-O2- cathode reduction system, several substrates such as cholesterol (1) and Grundmann's alcohol (3) gave the corresponding tertiary alcohols 2 and 4, respectively, in reasonable yield.
- Maki, Shojiro,Konno, Katsuhiro,Takayama, Hiroaki
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p. 7067 - 7070
(2007/10/03)
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- Cytotoxicity and suppression of immunoglobulin production against human Namalwa cells caused by oxidized cholesterol
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The effects of oxidized cholesterols on proliferation and IgM production of human lymphoblastoid Namalwa cells were examined. An oxidized cholesterol mixture, in contrast to cholesterol, was a potent cytotoxin to Namalwa cells. Among oxidized cholesterols examined, 25-hydroxycholesterol was the most cytotoxic. However, no oxidized cholesterol examined suppressed IgM production, although cholestanetriol and 7-ketocholesterol did suppress it. Thus, oxidized cholesterols are cytotoxic to lymphocytes, while the influence on the immunoglobulin production may be marginal.
- Osada, Kyoichi,Kodama, Takehiro,Matsuo, Noritaka,Yamada, Koji,Sugano, Michihiro
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p. 1362 - 1364
(2007/10/03)
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- Syntheses of Novel 25-Hydroxyvitamin D3 Haptens having Chemical Bridges at the C-11α Position
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The serum or plasma levels of 25-hydroxyvitamin D3 1a is useful for the evaluation of vitamin D status in various clinical or nutritional disorders.To obtain antibodies to compound 1a which are highly specific and useful for development of immunoassays, two novel haptenic derivatives, 11α-(3-carboxypropionyloxy)-25-hydroxyvitamin D3 2a and 11α-(4-carboxybutyryloxy)-25-hydroxyvitamin D3 2b were synthesized each in 21 steps from 11α-hydroxydehydroepiandrosterone 3.
- Kobayashi, Norihiro,Hisada, Akihiko,Shimada, Kazutake
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- METHYLATION AND HYDROXYMETHYLATION INVOLVING FREE RADICALS. AN APPLICATION TO STEREOSELECTIVE CONSTRUCTION OF 20(S) STEROL SIDE-CHAIN
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Reductive radical cyclization of bromomethyl-silyl-ethers 1b and 2b was found to proceed in 5-exo-mode.Epimeric cyclic siloxanes 3 were transformed stereoselectively into 20(S) 25-hydroxycholesterol.Unsaturated (E) ester 4 was converted to its (Z) isomer 7 via saturation and selective dehydrogenation.
- Kurek-Tyrlik, Alicja,Wicha, Jerzy,Snatzke, Guenther
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p. 4001 - 4004
(2007/10/02)
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- SYNTHETIC STUDIES ON VITAMIN D ANALOGUES VI. A NEW SYNTHESIS OF 25-HYDROXYCHOLESTEROL FROM LITHOCHOLIC ACID
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The conversion of lithocholic acid (1) into 25-hydroxycholesterol (10) via methyl 3β-hydroxy-5-cholenate (6) is described.
- Miyamoto, Katsuhito,Kubodera, Noboru,Murayama, Eigoro,Ochi, Kiyoshige,Mori, Takashi,Matsunaga, Isao
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p. 513 - 522
(2007/10/02)
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- Dienol Rearrangements Catalyzed by Nickel Chloride
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The rearrangement of dienols R2C(OH)CH=CHC(X)=CR2 which possess a nonterminal, arylthio or alkylthio substituent was effected by using nickel chloride in aqueous tert-butyl alcohol at 60 deg C to furnish the vicinally substituded dienol R2C=CHCH=C(X)CR2(OH).Application of this rearrangement to 24-(methylthio)cholesta-5,22,24-trien-20-ol provided 24-(methylthio)cholesta-5,20(22),23-trien-25-ol and formed the basis for a new, five-step synthesis of (20R)-25-hydroxycholesterol from pregnenolone tetrahydropyranyl ether.The rearrangement process appeared to be driven by the relief of unfavorable steric interactions between the quaternary C-13 and C-20 centers in steroids and influenced by the nature of the nickel(II) catalyst.The sulfur-containing substituent was not a prerequisite for the rearrangement since the desulfurized dienols underwent an analogous rearrangement.Preparation of these desulfurized dienols involved the use of a Raney nickel catalyst deactivated by heating in decalin.This catalyst selectively desulfurized vinyl thioethers to olefins.
- Kyler, Keith S.,Bashir-Hashemi, A.,Watt, David S.
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p. 1084 - 1090
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF STEROID SIDE CHAINS VIA ORGANOBORANES. STEREOSPECIFIC SYNTHESIS OF 20R- AND 20S-25-HYDROXYCHOLESTEROL.
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Both 20R- and 20S-25-hydroxycholesterol have been stereospecially prepared from readily avaible 3β-hydroxy-5-androsten-17-one.
- Midland, M. Mark,Kwon, Young C.
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p. 2077 - 2080
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF STEROID SIDE CHAIN; STEREOSELECTIVE SYNTHESES OF CHOLESTEROL AND 25-HYDROXYCHOLESTEROL
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Novel stereoselective method to introduce side chain onto 17-oxosteroids has been deviced, and using the method cholesterol and 25-hydroxycholesterol are synthesized.
- Ohmori, Masayuki,Yamada, Sachiko,Takayama, Hiroaki
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p. 4709 - 4712
(2007/10/02)
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- An Efficient Procedure for Preparing 1α,3β-Dihydroxy-Δ5-sterois by Reduction of 1α,2α-Epoxy-4,6-dien-3-ones with Lithium in Ammonia
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A number of 1α,3β-dihydroxy-Δ5-steroids of the cholestane, (20S)-20-methylpregnane (23,24-dinorcholane), pregnane and androstane series were synthesized from common steroidal precursors.A process originally reported by Barton et aI., based on 1,4,6-trien-3-ones as intermediates, was used for the introduction of the lα-hydroxyl function.The last step of this process, consisting of lithium/ammonia reduction of 1α,2α-epoxy-4,6-dien-3-ones, was found to be crucial and therefore subjected to particular study.A reproducible procedure permitting high-yield conversion was developed. lt consists of first reducing the epoxydienone with an approximately stoichiometric amount of lithium in ammonia to give, after protonation with ammonium chloride, a 1α-hydroxy-5-en-3-one.This intermediate is then further reduced by repeated alternating treatment with ammonium chloride and an equivalent amount of lithium.
- Fuerst, Andor,Labler, Ludvik,Meier, Werner
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p. 1870 - 1892
(2007/10/02)
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- A NEW SYNTHESIS OF 25-HYDROXYCHOLESTEROL
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A simple (η3-allyl)palladium-based synthesis of 25-hydroxycholesterol is described using a dimetallated coupling reagent.
- Riediker, Martin,Schwartz, Jeffrey
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p. 4655 - 4658
(2007/10/02)
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- Process for preparing 25-hydroxycholesterol
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The synthesis of 25-hydroxycholesterol and 25-hydroxycholecalciferol from animal bile starting materials in which hyodeoxycholic acid or an ester thereof is converted to the 3β-hydroxy-5-cholenic acid alkyl ester, and this is converted to 3β-hydroxy-25-cyano-5-cholene by a series of steps by which the sterol nucleus is stabilized by placing a protecting group at the 3 position and then extending the chain from the carbon at the 24 position to a cyanide group at the 25 position. The compound so formed is subjected to a series of reactions by which it is transformed into 25-hydroxy-7-dehydrocholesterol which may then be irradiated with ultraviolet light to 25-hydroxycholecalciferol. The invention discloses new and improved processes for preparing these end products and also new compounds formed as intermediates and processes for preparing these intermediates.
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- Synthesis of steroids
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The synthesis of 25-hydroxycholesterol and 1α,25-dihydroxycholesterol in which the sterol nucleus of an ester of hyodeoxycholic acid is stabilized by protection of the 3 and 6α-hydroxyl groups with alkyl groups, alkyl ether groups, preferably with the 3β-methoxyethoxymethyl group or with the heterocyclic 2-tetrahydropyran group, then extending the chain from the carbon at the 24-position to a cyanide group at the 25-position and then subjecting the sterol so formed to a series of reactions by which it is transformed into 1α,25-dihydroxycholesterol or by a modified series of reactions to 25-hydroxycholesterol.
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- Preparation of 3β-hydroxy-27-norcholest-5-ene-25-one and intermediates thereof
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A process for preparing 3β-hydroxy-27-norcholest-5-ene-25-one, a useful intermediate in the synthesis of 25-acetoxy vitamin D3, novel intermediates, and preparation thereof are disclosed.
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