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【结 构 式】 
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【药物名称】 【化学名称】Octadecanoyl-L-lysyl-L-lysyl-L-tyrosyl-L-leucinamide 【CA登记号】197907-73-6 【 分 子 式 】C45H81N7O6 【 分 子 量 】816.19062 |
【开发单位】Yeda (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, beta-Amyloid Protein Neurotoxicity Inhibitors |
合成路线1
The solid-phase method of peptide synthesis, with an ABIMED AMS 422 synthesizer and a Rink amide resin have been used. N-Fmoc-L-Leucine (I) was attached to Rink amide resin using benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate as the coupling reagent, and the Fmoc protecting group was subsequently removed to afford resin (II). Further coupling and deprotection cycles with N-Fmoc-L-tyrosine(O-t--Bu) (III), N-Fmoc-N-Boc-L-lysine (V) and again N-Fmoc-N-Boc-L-lysine (V) provided peptide resins (IV), (VI) and (VII), respectively.
| 【1】 Davidson, A.; Fridkin, M.; Perl, O.; Rubinraut, S.; Gozes, I.; Ashur-Fabian, O.; Giladi, E.; Mapping the active site in vasoactive intestinal to a core of four amino acids: Neuroprotective drug design. Proc Natl Acad Sci USA 1999, 96, 7, 4143. |
| 【2】 Gozes, I.; Fridkin, M. (Yeda Research & Development Co. Ltd.); Conjugates of lipophilic moieties and fragments of vasoactive intestinal peptide (VIP). WO 9740070 . |
| 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) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (II) | 27091 | (2S)-2-amino-4-methylpentanamide | C6H14N2O | 详情 | 详情 | |
| (III) | 18858 | (2S)-3-[4-(tert-butoxy)phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C28H29NO5 | 详情 | 详情 | |
| (IV) | 27096 | (2S)-2-([(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]amino)-4-methylpentanamide | C19H31N3O3 | 详情 | 详情 | |
| (V) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (VI) | 27092 | tert-butyl (5S)-5-amino-6-([(1S)-2-[[(1S)-1-(aminocarbonyl)-3-methylbutyl]amino]-1-[4-(tert-butoxy)benzyl]-2-oxoethyl]amino)-6-oxohexylcarbamate | C30H51N5O6 | 详情 | 详情 |
合成路线2
Peptide resin (VII) was then coupled with stearic acid to yield (VIII). Finally, the target peptide amide was deprotected and cleaved from the resin by means of a mixture of trifluoroacetic acid, water and triethylsilane.
| 【1】 Davidson, A.; Fridkin, M.; Perl, O.; Rubinraut, S.; Gozes, I.; Ashur-Fabian, O.; Giladi, E.; Mapping the active site in vasoactive intestinal to a core of four amino acids: Neuroprotective drug design. Proc Natl Acad Sci USA 1999, 96, 7, 4143. |
| 【2】 Gozes, I.; Fridkin, M. (Yeda Research & Development Co. Ltd.); Conjugates of lipophilic moieties and fragments of vasoactive intestinal peptide (VIP). WO 9740070 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 27095 | stearic acid | 57-11-4 | C18H36O2 | 详情 | 详情 |
| (VI) | 27092 | tert-butyl (5S)-5-amino-6-([(1S)-2-[[(1S)-1-(aminocarbonyl)-3-methylbutyl]amino]-1-[4-(tert-butoxy)benzyl]-2-oxoethyl]amino)-6-oxohexylcarbamate | C30H51N5O6 | 详情 | 详情 | |
| (VII) | 27093 | tert-butyl (5S)-5-amino-6-([(1S)-1-[([(1S)-2-[[(1S)-1-(aminocarbonyl)-3-methylbutyl]amino]-1-[4-(tert-butoxy)benzyl]-2-oxoethyl]amino)carbonyl]-5-[(tert-butoxycarbonyl)amino]pentyl]amino)-6-oxohexylcarbamate | C41H71N7O9 | 详情 | 详情 | |
| (VIII) | 27094 | tert-butyl (5S)-6-([(1S)-2-[[(1S)-1-(aminocarbonyl)-3-methylbutyl]amino]-1-[4-(tert-butoxy)benzyl]-2-oxoethyl]amino)-5-[[(2S)-6-[(tert-butoxycarbonyl)amino]-2-(stearoylamino)hexanoyl]amino]-6-oxohexylcarbamate | C59H105N7O10 | 详情 | 详情 |