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【结 构 式】 
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【分子编号】59882 【品名】3-({(1R,2R)-1-{1-[(2,2-dimethylpropanoyl)oxy]-2-propenyl}-2-hydroxy-6-[(4-methoxybenzyl)oxy]-4-hexynyl}oxy)propyl pivalate 【CA登记号】 |
【 分 子 式 】C30H44O8 【 分 子 量 】532.67456 【元素组成】C 67.65% H 8.33% O 24.03% |
合成路线1
该中间体在本合成路线中的序号：(XLV)Preparation of the allyl alcohol precursor (XXX) was further reported by an alternative method described in the two following schemes: The symmetrical epoxide (XXXV) was cleaved by 1,3-propanediol (II) in the presence of potassium tert-butoxide to give the diol (XXXVI). After protection of the primary alcohol of (XXXVI) as the pivalate ester (XXXVII), the benzyl ether groups of (XXXVII) were removed by hydrogenation in the presence of palladium hydroxide to provide (XXXVIII). Protection of the vicinal diol moiety of (XXXVII) as the corresponding acetonide (XXXIX) was achieved by treatment with 2,2-dimethoxypropane and p-TsOH. Subsequent Swern oxidation of the primary alcohol function of (XXXIX) gave aldehyde (XL). Addition of vinylmagnesium bromide to aldehyde (XL) afforded the allylic alcohol (XLI) as a diastereomeric mixture. Esterification of (XLI) with pivaloyl chloride provided dipivalate ester (XLII). Epoxide (XLIII) was then prepared by acidic acetonide (XLII) hydrolysis, followed by cyclization of the resultant vicinal diol under Mitsunobu conditions to afford epoxide (XLIII). Addition of the O-protected lithium acetylide (XLIV) to epoxide (XLIII) furnished the acetylene adduct (XLV)
| 【1】 Hatakeyama, S.; Ikeda, T.; Maeyama, J.; Esumi, T.; Iwabuchi, Y.; Irie, H.; Convergent synthesis of 1alpha, 25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71). Bioorg Med Chem Lett 1997, 7, 22, 2871. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 14685 | 1,3-propanediol; Trimethylene Glycol | 504-63-2 | C3H8O2 | 详情 | 详情 |
| (XXXV) | 25266 | benzyl [(2S,3S)-3-[(benzyloxy)methyl]oxiranyl]methyl ether; (2S,3S)-2,3-bis[(benzyloxy)methyl]oxirane | C18H20O3 | 详情 | 详情 | |
| (XXXVI) | 46308 | (2R,3S)-1,4-bis(benzyloxy)-3-(3-hydroxypropoxy)-2-butanol | C21H28O5 | 详情 | 详情 | |
| (XXXVII) | 46309 | 3-([(1S,2R)-3-(benzyloxy)-1-[(benzyloxy)methyl]-2-hydroxypropyl]oxy)propyl pivalate | C26H36O6 | 详情 | 详情 | |
| (XXXVIII) | 59880 | 3-{[(1S,2R)-2,3-dihydroxy-1-(hydroxymethyl)propyl]oxy}propyl pivalate | C12H24O6 | 详情 | 详情 | |
| (XXXIX) | 46310 | 3-([(1S)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl]oxy)propyl pivalate | C15H28O6 | 详情 | 详情 | |
| (XL) | 46311 | 3-([(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-oxoethyl]oxy)propyl pivalate | C15H26O6 | 详情 | 详情 | |
| (XLI) | 46312 | 3-([(1S)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxy-3-butenyl]oxy)propyl pivalate | C17H30O6 | 详情 | 详情 | |
| (XLII) | 59883 | 3-({(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-[(2,2-dimethylpropanoyl)oxy]-3-butenyl}oxy)propyl pivalate | C22H38O7 | 详情 | 详情 | |
| (XLIII) | 46314 | 3-([(1R)-2-[(2,2-dimethylpropanoyl)oxy]-1-[(2R)oxiranyl]-3-butenyl]oxy)propyl pivalate | C19H32O6 | 详情 | 详情 | |
| (XLIV) | 59881 | {3-[(4-methoxybenzyl)oxy]-1-propynyl}lithium | C11H11LiO2 | 详情 | 详情 | |
| (XLV) | 59882 | 3-({(1R,2R)-1-{1-[(2,2-dimethylpropanoyl)oxy]-2-propenyl}-2-hydroxy-6-[(4-methoxybenzyl)oxy]-4-hexynyl}oxy)propyl pivalate | C30H44O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLV)Basic hydrolysis of the pivalate esters of (XLV) followed by protection with tert-butyldimethylsilyl chloride provided the trisilylated derivative (XLVI). The p-methoxybenzyl protecting group of (XLVI) was then removed by treatment with DDQ, yielding (XLVII). Red-Al reduction of the propargyl alcohol (XLVII), followed by iodination produced the vinyl iodide (XLVIII). Intramolecular cyclization of iodide (XLVIII) under Heck reaction conditions gave rise to the key allyl alcohol intermediate (XXX), along with its undesired diastereoisomer (XLIX), which was separated by column chromatography
| 【1】 Hatakeyama, S.; Ikeda, T.; Maeyama, J.; Esumi, T.; Iwabuchi, Y.; Irie, H.; Convergent synthesis of 1alpha, 25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71). Bioorg Med Chem Lett 1997, 7, 22, 2871. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXX) | 59876 | 2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol | C60H74O5Si3 | 详情 | 详情 | |
| (XLV) | 59882 | 3-({(1R,2R)-1-{1-[(2,2-dimethylpropanoyl)oxy]-2-propenyl}-2-hydroxy-6-[(4-methoxybenzyl)oxy]-4-hexynyl}oxy)propyl pivalate | C30H44O8 | 详情 | 详情 | |
| (XLVI) | 59884 | (5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-8-nonen-2-ynyl 4-methoxybenzyl ether; (6R)-6-{(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-3-pentynyl}-2,2,3,3,12,12,13,13-octamethyl-5-vinyl-4,7,11-trioxa-3,12-disilatetradecane | C38H70O6Si3 | 详情 | 详情 | |
| (XLVII) | 59885 | (5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-8-nonen-2-yn-1-ol | C30H62O5Si3 | 详情 | 详情 | |
| (XLVIII) | 59886 | (2Z,5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-iodo-2,8-nonadien-1-ol | C30H63IO5Si3 | 详情 | 详情 | |
| (XLIX) | 59887 | 2-[(3S,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol | C60H74O5Si3 | 详情 | 详情 |