【结 构 式】 |
【分子编号】10646 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9-bis(benzyloxy)-15-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 【CA登记号】 |
【 分 子 式 】C45H50O11 【 分 子 量 】766.8854 【元素组成】C 70.48% H 6.57% O 22.95% |
合成路线1
该中间体在本合成路线中的序号:(XXIX)The intramolecular pinacolic cyclization of (XXI) by means of SmI2 yields the compound (XXII) with the basic ABC subskeleton of paclitaxel. Selective acetylation and silylation of (XXII) with acetic anhydride/pyridine and TBDMS-Cl gives the trihydroxy compound (XXIII), which is oxidized with oxalyl chloride as usual to the trione (XXIV). Selective reduction of (XXIV) with Zn(BH4)2 yields the dihydroxydione (XXV), which is selectively benzoylated and, after benzyl protection of the remaining hydroxy groups, affords the protected dione (XXVI). Selective reduction of (XXVI) with L-selectride followed by oxidation of the sulfanyl group to sulfinyl and its elimination by heating gives a methylene double bond, which is oxidized in situ with MCPBA and OsO4 to the vicinal triol (XXVII). The cyclization of (XXVII) according to Tetrahedron Lett 1991, 47: 9823 affords the hydroxy ketone (XXVIII) with the basic skeleton of paclitaxel. Acetylation of (XXVIII) with acetic anhydride/pyridine followed by selective elimination of the TBDMS group affords the secondary alcohol (XXIX). The attachment of the propenoyl side-chain of paclitaxel to (XXIX) according to J Amer Chem Soc 1988, 110: 5917 gives the protected paclitaxel derivative (XXX), which is finally deprotected by hydrogenolysis with H2 over Pd/C.
【1】 Danishefsky, S.J.; Bornmann, W.G.; Queneau, Y.; Magee, T.V.; Krol, W.J. (Sloan-Kettering Institute); Total synthesis of taxol. US 5416225 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXII) | 10639 | (1S,3R,4S,7S,8S,10R,13S)-7-(Benzyloxy)-1,2,5,10,13-pentahydroxy-8,12,15,15-tetramethyl-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-9-one | C33H42O7S | 详情 | 详情 | |
(XXIII) | 10640 | (1S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[[tert-butyl(dimethyl)silyl]oxy]-1,2,5-trihydroxy-8,12,15,15-tetramethyl-9-oxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate | C41H58O8SSi | 详情 | 详情 | |
(XXIV) | 10641 | (1S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-8,12,15,15-tetramethyl-2,5,9-trioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate | C41H54O8SSi | 详情 | 详情 | |
(XXV) | 10642 | (1S,2S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[[tert-butyl(dimethyl)silyl]oxy]-1,2-dihydroxy-8,12,15,15-tetramethyl-5,9-dioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate | C41H56O8SSi | 详情 | 详情 | |
(XXVI) | 10643 | (1S,2S,3R,4S,7S,8S,10R,13S)-10-(acetoxy)-1,7-bis(benzyloxy)-13-[[tert-butyl(dimethyl)silyl]oxy]-8,12,15,15-tetramethyl-5,9-dioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate | C55H66O9SSi | 详情 | 详情 | |
(XXVII) | 10644 | (1S,2S,3R,4S,5R,7S,8S,10R,13S)-10-(acetoxy)-1,7-bis(benzyloxy)-13-[[tert-butyl(dimethyl)silyl]oxy]-4,5-dihydroxy-4-(hydroxymethyl)-8,12,15,15-tetramethyl-9-oxotricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate | C49H64O11Si | 详情 | 详情 | |
(XXVIII) | 10645 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetoxy)-1,9-bis(benzyloxy)-15-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C49H62O10Si | 详情 | 详情 | |
(XXIX) | 10646 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9-bis(benzyloxy)-15-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C45H50O11 | 详情 | 详情 | |
(XXX) | 10647 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(2-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1,9-bis(benzyloxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C65H71NO15 | 详情 | 详情 |