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【结 构 式】

【分子编号】35343

【品名】(1S,5S,6R,7S,8S,12S,15S)-7,10,10,14,17,17-hexamethyl-3-oxo-15-[(triisopropylsilyl)oxy]-2,4,9,11-tetraoxatetracyclo[11.3.1.0(1,5).0(8,12)]heptadec-13-ene-6-carbaldehyde

【CA登记号】

【 分 子 式 】C29H48O7Si

【 分 子 量 】536.78142

【元素组成】C 64.89% H 9.01% O 20.86% Si 5.23%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XV)

The condensation of verbenone (I) with 1-bromo-3-methyl-2-butene (II) by means of t-BuOK in DME, followed by ozonolysis of the aliphatic double bond gives acetaldehyde (III), which is isomerized with UV light in methanol to the chrysanthenone derivative (IV). The condensation of (IV) with ethyl propynoate (V) by means of LDA in THF, followed by silylation with TMSCl affords the silylated 4-hydroxy-2-pentynoate (VI), which is cyclized by means of Me2CuLi in ethyl ether giving the methanonaphthalene derivative (VII). The oxidation of the secondary OH group of (VII) with Dess Martin periodinane (DMP) yields the ketoester (VIII), which is hydroxylated with Davis' oxaziridine to the ketonic dihydroxyester (IX). The reduction of the ester group of (IX) with LiAlH4 in ethyl ether affords the tetrahydroxy compound (X), which is protected by silylation with TBDMS-Cl and imidazole and ketalization with PPTS and 2-methoxypropene providing the silylated acetonide (XI). The rearrangement of (XI) by means of MCPBA, followed by silylation with Tips-OTf gives (XII) with the A-B-bicycle of Taxol. The hydroxylation of (XII) with t-BuOK and oxygen, followed by reduction of its ketonic group with NaBH4 yields the trihydroxy compound (XIII), which is stereoselectively reduced with H2 and Crabtree catalyst, silylated with TMSCl and treated with triphosgene to afford the cyclic carbonate (XIV). The oxidation of (XIV) with pyridinium chlorochromate (PCC) in dichloromethane gives the carbaldehyde (XV), which is condensed with methoxymethyl(triphenyl)phosphorane to yield the acetaldehyde derivative (XVI). The selective silylation of (XVI) with Tes-Cl, followed by oxidation of the remaining secondary OH group with Dess Martin periodinane (DMP) and methylenation acetaldehyde CH2 group with Me2N-CH2-I affords the substituted propenoic aldehyde (XVII).

1 Wender, P.A.; et al.; The pinene path to taxanes. 5. Stereocontrolled synthesis of a versatile taxane precursor. J Am Chem Soc 1997, 119, 11, 2755.
2 Wender, P.A.; et al.; The pinene path to taxanes. 6. Concise stereocontrolled synthesis of Taxol. J Am Chem Soc 1997, 119, 11, 2757.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
17354 isopropenyl methyl ether; 2-methoxy-1-propene 116-11-0 C4H8O 详情 详情
40589 methyl (triphenylphosphoranylidene)methyl ether; (methoxymethylene)(triphenyl)phosphorane C20H19OP 详情 详情
40590 iodo-N,N-dimethylmethanamine; N-(iodomethyl)-N,N-dimethylamine C3H8IN 详情 详情
(I) 35330 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one 1196-01-6 C10H14O 详情 详情
(II) 12989 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene 870-63-3 C5H9Br 详情 详情
(III) 35331 2-(2,6,6-trimethyl-4-oxobicyclo[3.1.1]hept-2-en-3-yl)acetaldehyde C12H16O2 详情 详情
(IV) 35332 2-(2,6,6-trimethyl-7-oxobicyclo[3.1.1]hept-2-en-1-yl)acetaldehyde C12H16O2 详情 详情
(V) 35333 ethyl propiolate 623-47-2 C5H6O2 详情 详情
(VI) 35334 ethyl 5-(2,6,6-trimethyl-7-oxobicyclo[3.1.1]hept-2-en-1-yl)-4-[(trimethylsilyl)oxy]-2-pentynoate C20H30O4Si 详情 详情
(VII) 35335 ethyl (6R)-3,6-dihydroxy-4,10,11,11-tetramethyltricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate C18H26O4 详情 详情
(VIII) 35336 ethyl (6R)-6-hydroxy-4,10,11,11-tetramethyl-3-oxotricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate C18H24O4 详情 详情
(IX) 35337 ethyl (2S,6R)-2,6-dihydroxy-4,10,11,11-tetramethyl-3-oxotricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate C18H24O5 详情 详情
(X) 35338 (2S,3S,6S)-5-(hydroxymethyl)-4,10,11,11-tetramethyltricyclo[5.3.1.0(1,6)]undeca-4,9-diene-2,3,6-triol C16H24O4 详情 详情
(XI) 35339 (2S,6S,9S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4,4,7,13,14,14-hexamethyl-3,5-dioxatetracyclo[8.3.1.0(1,9).0(2,6)]tetradeca-7,12-dien-9-ol C25H42O4Si 详情 详情
(XII) 35340 (2S,6S,12S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4,4,7,13,14,14-hexamethyl-12-[(triisopropylsilyl)oxy]-3,5-dioxatricyclo[8.3.1.0(2,6)]tetradeca-1(13),7-dien-9-one C34H62O5Si2 详情 详情
(XIII) 35341 (2S,6S,9S,10S,12S)-8-(hydroxymethyl)-4,4,7,13,14,14-hexamethyl-12-[(triisopropylsilyl)oxy]-3,5-dioxatricyclo[8.3.1.0(2,6)]tetradeca-1(13),7-diene-9,10-diol C28H50O6Si 详情 详情
(XIV) 35342 (1S,5S,6S,7S,8S,12S,15S)-7,10,10,14,17,17-hexamethyl-15-[(triisopropylsilyl)oxy]-6-[[(trimethylsilyl)oxy]methyl]-2,4,9,11-tetraoxatetracyclo[11.3.1.0(1,5).0(8,12)]heptadec-13-en-3-one C32H58O7Si2 详情 详情
(XV) 35343 (1S,5S,6R,7S,8S,12S,15S)-7,10,10,14,17,17-hexamethyl-3-oxo-15-[(triisopropylsilyl)oxy]-2,4,9,11-tetraoxatetracyclo[11.3.1.0(1,5).0(8,12)]heptadec-13-ene-6-carbaldehyde C29H48O7Si 详情 详情
(XVI) 35344 2-[(1S,5S,6R,7S,8S,9S,12S)-8,9-dihydroxy-7,11,14,14-tetramethyl-3-oxo-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]acetaldehyde C27H46O7Si 详情 详情
(XVII) 35345 2-[(1S,5S,6S,7S,8S,12S)-7,11,14,14-tetramethyl-3,9-dioxo-8-[(triethylsilyl)oxy]-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]acrylaldehyde C34H58O7Si2 详情 详情
Extended Information