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【结 构 式】

【药物名称】SB-T-1213

【化学名称】Benzoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-[3(S)-(tert-butoxycarbonylamino)-2(R)-hydroxy-5-methyl-4-hexenoyloxy]-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-6-(propionyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl ester
      3'-N-(tert-Butoxycarbonyl)-10-O-deacetyl-3'-N-debenzoyl-3'-dephenyl-3'-(2,2-dimethylvinyl)-10-O-(propionyl)paclitaxel

【CA登记号】

【 分 子 式 】C44H59NO15

【 分 子 量 】841.95853

【开发单位】State University of New York,Stony Brook (Originator)

【药理作用】ONCOLYTIC DRUGS, Taxanes

合成路线1

Lithium enolate (II), generated from chiral ester (I) and LDA at -84 C, was cyclocondensed with imine (III) to furnish azetidinone (IV). The N-p-methoxyphenyl group of (IV) was then removed by oxidative treatment with ceric ammonium nitrate at -10 C, and the resulting azetidinone (V) was protected with Boc2O to afford tert-butyl carbamate (VI).

1 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.
2 Takahashi, N.; et al.; Growth inhibition of gastric cancer cells by troglitazone, a ligand for peroxisome proliferator-activated receptor. Dig Dis Week (May 16 1999, Orlando) 1999, Abst 3684.
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) 21730 2-(Triisopropylsilyloxy)-1-(2(S)-phenyl-1(R)-cyclohexyl)vinyl-1-ol lithium salt C23H37LiO3Si 详情 详情
(IV) 21732 (3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone C22H35NO3Si 详情 详情
(V) 19156 (3R,4S)-4-(2-methyl-1-propenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone C16H31NO2Si 详情 详情
(VI) 19157 tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate C21H39NO4Si 详情 详情

合成路线2

The C-7 hydroxyl group of 10-deacetyl baccatin III (VII) was selectively protected with triethylsilyl chloride and imidazole to yield silyl ether (VIII). Subsequent selective acylation of (VIII) at C-10 hydroxyl group with propionyl chloride in the presence of LiN(SiMe3)2 afforded ester (IX). The title taxoid was then obtained by further coupling with b-lactam (VI) using LiN(SiMe3)2 in THF at low temperature, followed by desilylation with HF in pyridine.

1 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.
2 Takahashi, N.; et al.; Growth inhibition of gastric cancer cells by troglitazone, a ligand for peroxisome proliferator-activated receptor. Dig Dis Week (May 16 1999, Orlando) 1999, Abst 3684.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 19157 tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate C21H39NO4Si 详情 详情
(VII) 10467 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 32981-86-5 C29H36O10 详情 详情
(VIII) 21737 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C35H50O10Si 详情 详情
(IX) 10473 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C37H52O11Si 详情 详情
Extended Information