【结 构 式】 |
【分子编号】20873 【品名】benzyl 2-([5-amino-4-[(2-aminopropanoyl)amino]-5-oxopentanoyl]amino)-6-[[(benzyloxy)carbonyl]amino]hexanoate 【CA登记号】 |
【 分 子 式 】C29H39N5O7 【 分 子 量 】569.65816 【元素组成】C 61.15% H 6.9% N 12.29% O 19.66% |
合成路线1
该中间体在本合成路线中的序号:(VII)The condensation of tert-butoxycarbonyl-L-alanine (I) with benzyl D-isoglutaminate (II) by means of N-hydroxysuccinimide (NOHS) and dicyclohexylcarbodiimide (DCC) gives the protected dipeptide (III), which is hydrogenated with H2 over Pd/C in methanol yielding tert-butoxycarbonyl-D-isoglutaminyl-L-alanine (IV). The condensation of (IV) with Nepsilon-(benzyloxycarbonyl)-L-lysine benzyl ester (V) by means of ethyl chloroformate and triethylamine affords the protected tripeptide (VI), which is treated with trifluoroacetic acid (TFA) to afford L-alanyl-D-isoglutaminyl-(Nepsilon-benzyloxycarbonyl)-L-lysine benzyl ester (VII).
【1】 Shiba, T.; Yamamura, Y.; Nagase, O.; Kotani, S.; Ogawa, H. (Daiichi Seiyaku Co.; Ltd.); Muramyldipeptide derivatives, process for preparing said compounds and pharmaceutical compositions containing said compounds. EP 0021367 . |
【2】 Robinson, C.P.; MUROCTASIN. Drugs Fut 1989, 14, 5, 432. |
【3】 Shiba, T.; Kusumoto, S.; Tarumi, Y.; Ikenaka, K.; Chemical synthesis of N-acetylmuramyl peptides with partial structures of bacterial cell wall and their analogs in relation to immunoadjuvant activities. 1976, 49(2): 533-9. Bull Chem Soc Jpn 1976, 49, 2, 533. |
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) | 20337 | N-(tert-butoxycarbonyl)alanine | C8H15NO4 | 详情 | 详情 | |
(II) | 20868 | benzyl 4,5-diamino-5-oxopentanoate | C12H16N2O3 | 详情 | 详情 | |
(III) | 20869 | benzyl 5-amino-4-([2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-5-oxopentanoate | C20H29N3O6 | 详情 | 详情 | |
(IV) | 20870 | 5-amino-4-([2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-5-oxopentanoic acid | C13H23N3O6 | 详情 | 详情 | |
(V) | 20871 | benzyl 2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate | C21H26N2O4 | 详情 | 详情 | |
(VI) | 20872 | benzyl 9-(aminocarbonyl)-14-(4-[[(benzyloxy)carbonyl]amino]butyl)-2,2,6-trimethyl-4,7,12-trioxo-3-oxa-5,8,13-triazapentadecan-15-oate | C34H47N5O9 | 详情 | 详情 | |
(VII) | 20873 | benzyl 2-([5-amino-4-[(2-aminopropanoyl)amino]-5-oxopentanoyl]amino)-6-[[(benzyloxy)carbonyl]amino]hexanoate | C29H39N5O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(VII)The condensation of (VII) with 1-O-benzyl-4,6-O-benzylidene-N-acetylmuramic acid (VIII) by means of NOHS and DCC as before gives the protected muramyl tripeptide (IX) , which is treated with acetic acid yielding the partially protected compound (X).
【1】 Shiba, T.; Yamamura, Y.; Nagase, O.; Kotani, S.; Ogawa, H. (Daiichi Seiyaku Co.; Ltd.); Muramyldipeptide derivatives, process for preparing said compounds and pharmaceutical compositions containing said compounds. EP 0021367 . |
【2】 Robinson, C.P.; MUROCTASIN. Drugs Fut 1989, 14, 5, 432. |
【3】 Shiba, T.; Kusumoto, S.; Tarumi, Y.; Ikenaka, K.; Chemical synthesis of N-acetylmuramyl peptides with partial structures of bacterial cell wall and their analogs in relation to immunoadjuvant activities. 1976, 49(2): 533-9. Bull Chem Soc Jpn 1976, 49, 2, 533. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VII) | 20873 | benzyl 2-([5-amino-4-[(2-aminopropanoyl)amino]-5-oxopentanoyl]amino)-6-[[(benzyloxy)carbonyl]amino]hexanoate | C29H39N5O7 | 详情 | 详情 | |
(VIII) | 20874 | 2-[[7-(acetamido)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propionic acid | C25H29NO8 | 详情 | 详情 | |
(IX) | 20875 | benzyl 2-[[4-([2-[(2-[[7-(acetamido)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propanoyl)amino]propanoyl]amino)-5-amino-5-oxopentanoyl]amino]-6-[[(benzyloxy)carbonyl]amino]hexanoate | C54H66N6O14 | 详情 | 详情 | |
(X) | 20876 | benzyl 2-[[4-([2-[(2-[[3-(acetamido)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy]propanoyl)amino]propanoyl]amino)-5-amino-5-oxopentanoyl]amino]-6-[[(benzyloxy)carbonyl]amino]hexanoate | C47H62N6O14 | 详情 | 详情 |