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【结 构 式】 
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【分子编号】15008 【品名】(4R,5S)-3-[3-((1S,3R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C36H45NO5Si 【 分 子 量 】599.84254 【元素组成】C 72.08% H 7.56% N 2.34% O 13.34% Si 4.68% |
合成路线1
该中间体在本合成路线中的序号：(XX)Intermediate (II): Compound (II) is obtained starting from two new previously synthesized intermediates, the oxazolidinone (XX) (scheme 17565203d) and the aldehyde (XXI) (scheme 17565203e), which are condensed by means of dibutylboron trifluoromethanesulfonate in dichloromethane to give compound (XXII), which is reduced first with LiBH4, tosylated with tosyl chloride and reduced again with lithium triethylborohydride in THF to yield compound (XXIII). The esterification of (XXIII) with the piperidine-2-carboxylic acid (XXIV) by means of DIC in dichloromethane followed by iodination of the terminal vinyl group by means of OsO4-catalyzed diol formation - Pb(OAc)4 cleavage, followed by CrCl2-mediated iodo-olefination with triiodomethane in THF/dioxane, affords the iodovinyl ester (XXV). Finally, (XXV) is debenzylated with DDQ in CHCl3 and silylated with triethylsilyl trifluoromethanesulfonate in dichloromethane to afford intermediate (II) (see K.C. Nicolau et al., J Chem Soc Chem Commun 1993, 7: 619). (1,2)
| 【1】 Nicolaou, K.C.; Piscopio, A.D.; Bertinato, P.; Chakraborty, T.K.; Minowa, N.; Koide, K.; Total Synthesis of Rapamycin. Chemistry (Weinheim) 1995, 1, 5, 318. |
| 【2】 Nicolaou, K.C.; Chakraborty, T.K.; Piscopio, A.D.; Minowa, N.; Bertinato, P.; Total synthesis of rapamycin. J Am Chem Soc 1993, 115, 10, 4419. |
| 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) | 14990 | (1S,3S,4R,5E,7R,8R,9R,10R,12S,13E)-1-[(1R)-2-((1S,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethyl]-14-iodo-8-methoxy-4,6,10,12-tetramethyl-3,9-bis(triethylsilyl)-7-[(triisopropylsilyl)oxy]-5,13-tetradecadienyl (2S)-2-piperidinecarboxylate | C72H128INO6Si4 | 详情 | 详情 | |
| (XX) | 15008 | (4R,5S)-3-[3-((1S,3R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one | C36H45NO5Si | 详情 | 详情 | |
| (XXI) | 15009 | (3S,4R,5E,7R,8S,9R,10R,12S)-8-methoxy-3,9-bis[(4-methoxybenzyl)oxy]-4,6,10,12-tetramethyl-7-[(triisopropylsilyl)oxy]-5,13-tetradecadienal | C44H70O7Si | 详情 | 详情 | |
| (XXII) | 15010 | (4R,5S)-3-[(2R,3S,5S,6R,7E,9R,10S,11R,12R,14S)-2-[((1S,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)methyl]-3-hydroxy-10-methoxy-5,11-bis[(4-methoxybenzyl)oxy]-6,8,12,14-tetramethyl-9-[(triisopropylsilyl)oxy]-7,15-hexadecadienoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one | C80H115NO12Si2 | 详情 | 详情 | |
| (XXIII) | 15011 | (2R,3S,5S,6R,7E,9R,10S,11R,12R,14S)-1-((1S,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-10-methoxy-5,11-bis[(4-methoxybenzyl)oxy]-2,6,8,12,14-pentamethyl-9-[(triisopropylsilyl)oxy]-7,15-hexadecadien-3-ol | C70H108O9Si2 | 详情 | 详情 | |
| (XXIV) | 11487 | (2S)-1-(tert-Butoxycarbonyl)hexahydro-2-pyridinecarboxylic acid | C11H19NO4 | 详情 | 详情 | |
| (XXV) | 15013 | 1-(tert-butyl) 2-[(1S,3S,4R,5E,7R,8S,9R,10R,12S,13E)-1-[(1R)-2-((1S,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethyl]-14-iodo-8-methoxy-3,9-bis[(4-methoxybenzyl)oxy]-4,6,10,12-tetramethyl-7-[(triisopropylsilyl)oxy]-5,13-tetradecadienyl] (2S)-1,2-piperidinedicarboxylate | C81H124INO12Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XX)The new intermediates, the oxazolidinone (XX) and the aldehyde (XXI), are obtained as follows: Oxazolidinone (XX): The ring opening of cyclohexane epoxide (XXVI) with methanol and CSA followed by silylation with tert-butyldimethylsilyl trifluoromethanesulfonate in dichloromethane gives compound (XXVII), which is debenzylated by hydrogenolysis and oxidized with oxalyl chloride to the cyclohexanone (XXVIII). Dehydrogenation of (XXVIII) by treatment with lithium diiosopropylamide (LDA), tosyl chloride and palladium diacetate yields the cyclohexenone (XXIX), which is reduced with LiBH4 - CeCl3 in methanol/THF to the cyclohexenol (XXX). The condensation of (XXX) with dimethylacetamide diethylacetal (XXXI) in refluxing xylene affords the cyclohexylacetamide (XXXII), which is reduced with lithium triethylborohydride in THF and with H2 over Pd/C in ethanol to give the cyclohexylethanol (XXXIII). The dehydration of (XXXIII) through a selenium derivative yields the vinyl compound (XXXIV), which is oxidized with ozone to the aldehyde (XXXV). Finally, the condensation of (XXXV) with the phosphonate (XXXVI) by means of IEN and LiCl in acetonitrile followed by a desilylation with HF and silylation with tert-butyldiphenylsilyl chloride in DMF yields the oxazolidinone (XX) (see K.C. Nicolau et al., J Chem Soc Chem Commun 1993, 7: 619). (1,2)
| 【1】 Nicolaou, K.C.; Piscopio, A.D.; Bertinato, P.; Chakraborty, T.K.; Minowa, N.; Koide, K.; Total Synthesis of Rapamycin. Chemistry (Weinheim) 1995, 1, 5, 318. |
| 【2】 Nicolaou, K.C.; Chakraborty, T.K.; Piscopio, A.D.; Minowa, N.; Bertinato, P.; Total synthesis of rapamycin. J Am Chem Soc 1993, 115, 10, 4419. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 15008 | (4R,5S)-3-[3-((1S,3R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one | C36H45NO5Si | 详情 | 详情 | |
| (XXVI) | 15014 | benzyl (1S,2R,6S)-7-oxabicyclo[4.1.0]hept-2-yl ether; (1S,2R,6S)-2-(benzyloxy)-7-oxabicyclo[4.1.0]heptane | C13H16O2 | 详情 | 详情 | |
| (XXVII) | 15015 | benzyl (1R,2S,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexyl ether; [[(1S,2R,6R)-2-(benzyloxy)-6-methoxycyclohexyl]oxy](tert-butyl)dimethylsilane | C20H34O3Si | 详情 | 详情 | |
| (XXVIII) | 15016 | (2S,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexanone | C13H26O3Si | 详情 | 详情 | |
| (XXIX) | 15017 | (5R,6S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methoxy-2-cyclohexen-1-one | C13H24O3Si | 详情 | 详情 | |
| (XXX) | 15018 | (1S,5R,6R)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methoxy-2-cyclohexen-1-ol | C13H26O3Si | 详情 | 详情 | |
| (XXXI) | 15019 | N-(1,1-diethoxyethyl)-N,N-dimethylamine; 1,1-diethoxy-N,N-dimethyl-1-ethanamine | C8H19NO2 | 详情 | 详情 | |
| (XXXII) | 15020 | 2-((1R,3R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexyl)-N,N-dimethylacetamide | C17H35NO3Si | 详情 | 详情 | |
| (XXXIII) | 15021 | 2-((1S,3R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexyl)-1-ethanol | C15H32O3Si | 详情 | 详情 | |
| (XXXIV) | 15022 | tert-butyl(dimethyl)silyl (1R,2R,4R)-2-methoxy-4-vinylcyclohexyl ether; tert-butyl[[(1R,2R,4R)-2-methoxy-4-vinylcyclohexyl]oxy]dimethylsilane | C15H30O2Si | 详情 | 详情 | |
| (XXXV) | 15023 | (1R,3R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexanecarbaldehyde | C14H28O3Si | 详情 | 详情 | |
| (XXXVI) | 15024 | diethyl 2-[(4R,5S)-4-methyl-2-oxo-5-phenyl-1,3-oxazolan-3-yl]-2-oxoethylphosphonate | C16H22NO6P | 详情 | 详情 |