• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】10561

【品名】(1S)-1-[(1R,4R,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8,11,11-tetramethyl-3-oxo-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-4-yl]-4-pentenyl propionate

【CA登记号】

【 分 子 式 】C35H64O5Si2

【 分 子 量 】621.06116

【元素组成】C 67.69% H 10.39% O 12.88% Si 9.04%

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:(VI)

The first part of a total synthesis of paclitaxel has been published: The silylation of tricyclic diol (I) (readily available from camphor) with triethylsilyl chloride (TESCl) gives compound (II), which is submitted to epoxy alcohol fragmentation followed by silylation to yield the silylated cyclic ketone (III). The magnesium enolate of (III) is submitted to an aldol condensation with 4-pentenal (IV) to afford the ketol (V), which is protected with COCl2 and EtOH, giving the carbonate ester (VI). The hydroxylation of (VI) with lithium diisopropylamide (LDA) and (+)-camphorsulfonyl oxaziridine (VII) yields the alpha-hydroxy ketone (VIII), which is reduced with Red-Al in toluene, affording the alpha-diol (IX). The reaction of (IX) with COCl2 in pyridine gives the cyclic carbonate (X), which is oxidized with the Swern oxidant to the ketone (XI). The rearrangement of (XI) with lithium 2,2,6,6-tetramethylpiperidide (LTMP) yields the hydroxy lactone (XII), which is reduced with samarium diiodide to the stable enol (XIII), which by treatment with silica gel gives a mixture of cis- and trans-oxolactones (cis-XIV + trans-XIV) that can be separated by crystallization. (trans-XIV) does not react with LTMP, but can be reverted to (XIII) with t-BuOK in order to increase the yield in (cis-XIV). On the other hand, the reaction of (cis-XIV) with LTMP and (+)-camphorsulfonyl oxaziridine (VII) affords a mixture of cis- and trans-hydroxy-oxolactones (cis-XV + trans-XV) that can be separated by chromatography. The reduction of (cis-XV) with Red-Al followed by a basic workup gives the alpha-diol with trans-configuration in the lactone ring (XVI), and the reduction of (trans-XV) with samarium diiodide affords the same alpha-diol isomer (XVI). This alpha-diol (XVI) is protected with COCl2 in pyridine to give the cyclic carbonate (XVII). (For the second part, see Holton, R.A. et al. J Amer Chem Soc 1994, 116(4): 1599).

1 Kim, H.-B.; Somoza, C.; Holton, R.A.; et al.; First total synthesis of taxol. 1. Functionalization of the B ring. J Am Chem Soc 1994, 116, 4, 1597.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(trans-XIV) 10569 (1S,3R,6S,7S,9R,12S)-6-(3-Butenyl)-12-[[tert-butyl(dimethyl)silyl]oxy]-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione C33H58O5Si2 详情 详情
(cis-XIV) 10570 (1S,3S,6S,7S,9R,12S)-6-(3-Butenyl)-12-hydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione C33H58O5Si2 详情 详情
(trans-XV) 10571 (1S,3R,6S,7S,9R,12S)-6-(3-Butenyl)-1,12-dihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione C33H58O6Si2 详情 详情
(cis-XV) 10572 (1S,3R,6S,7S,9R,12S)-6-(3-Butenyl)-1,12-dihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione C33H58O6Si2 详情 详情
(I) 10556 (2R,4R,5S)-4,10,11,11-Tetramethyltricyclo[5.3.1.0(1,5)]undec-9-ene-2,5-diol C15H24O2 详情 详情
(II) 10557 (2R,4R,5S)-4,10,11,11-Tetramethyl-2-[(triethylsilyl)oxy]tricyclo[5.3.1.0(1,5)]undec-9-en-5-ol C21H38O2Si 详情 详情
(III) 10558 (1R,4R,6R,9S)-9-[[tert-Butyl(dimethyl)silyl]oxy]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-3-one C27H52O3Si2 详情 详情
(IV) 10559 4-Pentenal 2100-17-6 C5H8O 详情 详情
(V) 10560 (1R,4R,6R,9S)-9-[[tert-Butyl(dimethyl)silyl]oxy]-4-[(1S)-1-hydroxy-4-pentenyl]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-3-one C32H60O4Si2 详情 详情
(VI) 10561 (1S)-1-[(1R,4R,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8,11,11-tetramethyl-3-oxo-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-4-yl]-4-pentenyl propionate C35H64O5Si2 详情 详情
(VII) 10562 7,7-Dimethyl-1-[(1,2-oxaziran-2-ylsulfonyl)methyl]bicyclo[2.2.1]heptan-2-one C11H17NO4S 详情 详情
(VIII) 10563 (1S)-1-[(1S,2R,4R,6R,9S)-2,9-dihydroxy-4,8,11,11-tetramethyl-3-oxo-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-4-yl]-4-pentenyl propionate C35H64O6Si2 详情 详情
(IX) 10564 (1S,2R,3S,4R,6R,9S)-4-[(1S)-1-Hydroxy-4-pentenyl]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-ene-2,3,9-triol C32H62O5Si2 详情 详情
(X) 10565 (1S,2R,3S,7S,8S,10R,13S)-7-(3-Butenyl)-2,13-dihydroxy-8,12,15,15-tetramethyl-10-[(triethylsilyl)oxy]-4,6-dioxatricyclo[9.3.1.0(3,8)]pentadec-11-en-5-one C33H60O6Si2 详情 详情
(XI) 10566 (1S,3S,7S,8S,10R,13S)-7-(3-Butenyl)-13-[[tert-butyl(dimethyl)silyl]oxy]-8,12,15,15-tetramethyl-10-[(triethylsilyl)oxy]-4,6-dioxatricyclo[9.3.1.0(3,8)]pentadec-11-ene-2,5-dione C33H58O6Si2 详情 详情
(XII) 10567 (1S,3S,7S,8S,10R,13S)-7-(3-Butenyl)-13-hydroxy-8,12,15,15-tetramethyl-10-[(triethylsilyl)oxy]-4,6-dioxatricyclo[9.3.1.0(3,8)]pentadec-11-ene-2,5-dione C33H58O6Si2 详情 详情
(XIII) 10568 (1S,6S,7S,9R,12S)-6-(3-Butenyl)-2,12-dihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradeca-2,10-dien-4-one C33H58O5Si2 详情 详情
(XVI) 10573 (1S,3S,6S,7S,9R,12S)-6-(3-Butenyl)-1,12-dihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione C33H58O6Si2 详情 详情
(XVII) 10574 (1S,2S,3R,6S,7S,9R,12S)-6-(3-Butenyl)-1,2,12-trihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-en-4-one C33H60O6Si2 详情 详情
Extended Information