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【结 构 式】 
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【药物名称】 【化学名称】[2aR,4S,4aS,6R,9S(2R,3S),11S,12S,12aR,12bS]-6,12b-Diacetoxy-9-(3-benzamido-2-hydroxy-3-phenylpropionyloxy)-12-benzoyloxy-4-[2-[N,N-bis[2-[4-[4-[N,N-bis(2-chloroethyl)amino]phenyl]butyryloxy]ethyl]amino]acetoxymethoxy]-11-hydroxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-5-one 【CA登记号】340722-62-5 【 分 子 式 】C82H98Cl4N4O20 【 分 子 量 】1601.52216 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Taxanes |
合成路线1
The reaction of 2'-O-(triethylsilyl)paclitaxel (I) with dimethyl sulfide (DMS) and Bz2O2 in acetonitrile gives the 7-O-(methylsulfanylmethyl) derivative (II), which is condensed with chloroacetic acid (III) by means of N-iodosuccinimide (NIS) and Ag-OTf in THF to yield the 7-O-(chloroacetoxymethyl) derivative (IV). The desilylation of (IV) by means of HCl in acetonitrile affords the intermediate (V), which is finally condensed with the secondary amine (VI) by means of NaI in acetone to provide the target hybrid molecule.
| 【1】 Long, B.H.; Vyas, D.M.; Fairchild, C.; Kadow, J.F.; Rose, W.C.; Johnston, K.; Wittman, M.D.; Lee, F.L.; Synthesis and antitumor activity of novel paclitaxel-chlorambucil hybrids. Bioorg Med Chem Lett 2001, 11, 6, 811. |
| 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) | 49369 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)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 benzoate | C53H65NO14Si | 详情 | 详情 | |
| (II) | 49370 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-9-[(methylsulfanyl)methoxy]-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C55H69NO14SSi | 详情 | 详情 | |
| (III) | 11847 | 2-Chloroacetic acid; Chloroacetic Acid | 79-11-8 | C2H3ClO2 | 详情 | 详情 |
| (IV) | 49371 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-9-[[(2-chloroacetyl)oxy]methoxy]-1-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 | C56H68ClNO16Si | 详情 | 详情 | |
| (V) | 49372 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-9-[[(2-chloroacetyl)oxy]methoxy]-1-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 | C50H54ClNO16 | 详情 | 详情 | |
| (VI) | 49373 | 2-([2-[(4-[4-[bis(2-chloroethyl)amino]phenyl]butanoyl)oxy]ethyl]amino)ethyl 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoate | C32H45Cl4N3O4 | 详情 | 详情 |