|
【结 构 式】 
|
【分子编号】58361 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-[(3-methyl-3-sulfanylbutanoyl)oxy]-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 】C55H60Cl3NO17S 【 分 子 量 】1145.50204 【元素组成】C 57.67% H 5.28% Cl 9.28% N 1.22% O 23.74% S 2.8% |
合成路线1
该中间体在本合成路线中的序号：(V)Paclitaxel (I) is selectively protected at the side-chain hydroxyl group with 2,2,2-trichloroethyl chloroformate in pyridine to afford the carbonate ester (II). Subsequent acylation of (II) with 3-methyl-3-[(2,4,6-trimethoxybenzyl)thio]butyric acid (III) provides ester (IV). Removal of the trimethoxybenzyl protecting group of (IV) by means of formic acid in the presence of L-cysteine gives rise to thiol (V).
| 【1】 Lin, C.-E.; et al.; Design and synthesis of nitrosylated paclitaxel (NO-paclitaxel) and adamantanyl nitric oxide donor as antirestenosis agents. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 36. |
| 【2】 Garvey, D.S.; Letts, L.G.; Wang, T.; Richardson, S.K.; Lin, C.-E. (NitroMed Inc.); Nitrosated and nitrosylated taxanes, compsns. and methods of use. WO 0198286 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10595 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | 33069-62-4 | C47H51NO14 | 详情 | 详情 |
| (II) | 58359 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl | C50H52Cl3NO16 | 详情 | 详情 | |
| (III) | 38878 | 3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid | C15H22O5S | 详情 | 详情 | |
| (IV) | 58360 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-({3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl}oxy)-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C65H72Cl3NO20S | 详情 | 详情 | |
| (V) | 58361 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-[(3-methyl-3-sulfanylbutanoyl)oxy]-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C55H60Cl3NO17S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The trichloroethyl carbonate ester of (V) is then reductively cleaved using zinc dust and HOAc, to produce (VI). Finally, nitrosation of the thiol group of (VI) by means of t-butyl nitrite furnishes the target nitrosothio derivative.
| 【1】 Lin, C.-E.; et al.; Design and synthesis of nitrosylated paclitaxel (NO-paclitaxel) and adamantanyl nitric oxide donor as antirestenosis agents. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 36. |
| 【2】 Garvey, D.S.; Letts, L.G.; Wang, T.; Richardson, S.K.; Lin, C.-E. (NitroMed Inc.); Nitrosated and nitrosylated taxanes, compsns. and methods of use. WO 0198286 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 58361 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-[(3-methyl-3-sulfanylbutanoyl)oxy]-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C55H60Cl3NO17S | 详情 | 详情 | |
| (VI) | 58362 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-9-[(3-methyl-3-sulfanylbutanoyl)oxy]-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C52H59NO15S | 详情 | 详情 |