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【结 构 式】 
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【药物名称】GS-2888 【化学名称】Nomega-(tert-Butoxycarbonyl)-L-arginyl-glycine ditetradecylamide dihydrochloride 【CA登记号】175969-22-9 【 分 子 式 】C41H84Cl2N6O4 【 分 子 量 】796.07043 |
【开发单位】Gilead (Originator), GlaxoSmithKline (Originator) 【药理作用】Absorption Promoters, DRUG DELIVERY, Drug Delivery Systems, Pharmaceutical Aids |
合成路线1
Benzyloxycarbonylglycine (I) was coupled with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide (DCC), and the resulting succinimidyl active ester (II) was condensed with dimiristylamine (III) to afford amide (IV). The benzyloxycarbonyl group was then removed by hydrogenolysis in the presence of palladium on carbon to yield amine (V). Coupling of this amine with Boc-protected L-arginine (VI) in the presence of diisopropylcarbodiimide (DIC) gave dipeptide (VII). Finally, partial deprotection of Boc groups with hydrochloric acid in dioxane provided the title compound.
| 【1】 Lewis, J.G.; et al.; A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci USA 1996, 93, 8, 3177. |
| 【2】 Deprince, R.B.; Facchine, K.L.; Lewis, G.S.; Lewis, J.G.; Lin, K.-Y.; Matteucci, M.D.; Mook, R.A. Jr.; Wagner, R.W. (Gilead Sciences Inc.; Glaxo Wellcome plc); Cationic lipids for delivery of nucleic acids to cells. WO 9601841 . |
| 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) | 17764 | N-Carbobenzyloxyglycine; 2-[[(benzyloxy)carbonyl]amino]acetic acid | 1138-80-3 | C10H11NO4 | 详情 | 详情 |
| (II) | 17765 | benzyl 2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethylcarbamate; Z-glycine N-succinimidyl ester | 2899-60-7 | C14H14N2O6 | 详情 | 详情 |
| (III) | 17766 | DITETRADECYLAMINE; N-tetradecyl-1-tetradecanamine; N,N-ditetradecylamine | 17361-44-3 | C28H59N | 详情 | 详情 |
| (IV) | 17767 | benzyl 2-(ditetradecylamino)-2-oxoethylcarbamate | C38H68N2O3 | 详情 | 详情 | |
| (V) | 17768 | 2-amino-N,N-ditetradecylacetamide | C30H62N2O | 详情 | 详情 | |
| (VI) | 17769 | (2S)-2-[(tert-butoxycarbonyl)amino]-5-[(tert-butoxycarbonyl)[imino(methylamino)methyl]amino]pentanoic acid | C17H32N4O6 | 详情 | 详情 | |
| (VII) | 17770 | tert-butyl (4S)-4-[(tert-butoxycarbonyl)amino]-5-[[2-(ditetradecylamino)-2-oxoethyl]amino]-5-oxopentyl[[(tert-butoxycarbonyl)amino](imino)methyl]carbamate | C51H98N6O8 | 详情 | 详情 |