【结 构 式】 |
【分子编号】51201 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 【CA登记号】 |
【 分 子 式 】C47H78O10Si3 【 分 子 量 】887.38682 【元素组成】C 63.62% H 8.86% O 18.03% Si 9.49% |
合成路线1
该中间体在本合成路线中的序号:(XV)10-Deacetylbaccatin III (XIV) was protected by treatment with triethylsilyl chloride and imidazole, and the resulting trisilylated compound (XV) was debenzoylated to diol (XVI) by using Red-Al(R). Selective coupling of (XVI) with m-anisic acid (XVII) yielded the m-methoxybenzoate ester (XVIII). Complete desilylation of (XVIII) with HF-pyridine, followed by selective resilylation at C-7, furnished (XIX). The 10-hydroxyl group was then selectively acylated with p-methoxyphenylacetyl chloride (XX) to afford ester (XXI). Finally, coupling of the modified baccatin (XXI) with the intermediate lactam (XIII) in the presence of lithium hexamethyldisilazide, and then deprotection with HF-pyridine, gave rise to the desired taxoid.
【1】 Strum, M.; Tynebor, R.; Pera, P.; Bernacki, R.J.; Ojima, I.; Synthesis and SAR of advanced second generation taxoids. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 132. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XIII) | 19157 | tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate | C21H39NO4Si | 详情 | 详情 | |
(XIV) | 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 |
(XV) | 51201 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H78O10Si3 | 详情 | 详情 | |
(XVI) | 51202 | (1S,2S,3R,7R,9S,10S,12R,15S)-1,2-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-4-yl acetate | C40H74O9Si3 | 详情 | 详情 | |
(XVII) | 28559 | m-Anisic acid; 3-Methoxybenzoic acid | 586-38-9 | C8H8O3 | 详情 | 详情 |
(XVIII) | 51203 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate | C48H80O11Si3 | 详情 | 详情 | |
(XIX) | 51204 | (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 3-methoxybenzoate | C36H52O11Si | 详情 | 详情 | |
(XX) | 26758 | 2-(4-methoxyphenyl)acetyl chloride | 4693-91-8 | C9H9ClO2 | 详情 | 详情 |
(XXI) | 51213 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-12-[[2-(4-methoxyphenyl)acetyl]oxy]-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 3-methoxybenzoate | C45H60O13Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)10-Deacetylbaccatin III (I) was protected by treatment with triethylsilyl chloride and imidazole, and the resulting trisilylated compound (II) was debenzoylated to diol (III) by using Red-Al(R). Coupling of (III) with m-anisic acid (IV) yielded the m-methoxybenzoate ester (V). Complete desilylation of (V), followed by selective resilylation at C-7 with triethylsilyl chloride, furnished (VI). Acylation at C-10 and C-13 by means of Ac2O and DMAP, followed by desilylation, gave the modified baccatin (VII).
【1】 Strum, M.; et al.; Synthesis and SAR of new taxane reversal agents. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 131. |
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) | 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 |
(II) | 51201 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H78O10Si3 | 详情 | 详情 | |
(III) | 51202 | (1S,2S,3R,7R,9S,10S,12R,15S)-1,2-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-4-yl acetate | C40H74O9Si3 | 详情 | 详情 | |
(IV) | 28559 | m-Anisic acid; 3-Methoxybenzoic acid | 586-38-9 | C8H8O3 | 详情 | 详情 |
(V) | 51203 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate | C48H80O11Si3 | 详情 | 详情 | |
(VI) | 51204 | (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 3-methoxybenzoate | C36H52O11Si | 详情 | 详情 | |
(VII) | 51205 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-tris(acetoxy)-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 3-methoxybenzoate | C34H42O13 | 详情 | 详情 |