|
【结 构 式】 
|
【分子编号】56354 【品名】2,3,4,5,6-pentafluorophenyl (2R)-2-{[(3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoate 【CA登记号】 |
【 分 子 式 】C25H31F5N2O13 【 分 子 量 】662.518836 【元素组成】C 45.32% H 4.72% F 14.34% N 4.23% O 31.39% |
合成路线1
该中间体在本合成路线中的序号：(XXXVI)A more direct procedure was based on the activation of the unprotected disaccharide acid (XXXVI) as the pentafluorophenyl ester (XXXVII) by treatment with bis(pentafluorophenyl) carbonate. Active ester (XXXVII) was subsequently coupled with L-alanyl-D-isoglutamine (XXXVIII) to afford the corresponding amide.
| 【1】 Andronova, T.M.; et al.; Bacterial cell wall glycopeptides as adjuvants. Colloq INSERM 1989, 174, 561. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVI) | 56354 | 2,3,4,5,6-pentafluorophenyl (2R)-2-{[(3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoate | C25H31F5N2O13 | 详情 | 详情 | |
| (XXXVII) | 56355 | (4R)-5-amino-4-{[(2S)-2-aminopropanoyl]amino}-5-oxopentanoic acid | C8H15N3O4 | 详情 | 详情 | |
| (XXXVIII) | 56356 | (2R,3S,4R,5R,6S)-3-(acetyloxy)-2-[(acetyloxy)methyl]-6-chloro-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-4-yl acetate | C20H20ClNO9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVI)The disaccharide derivative (XXXVI) was isolated from the enzymatic hydrolysis of the cell walls obtained from cultures of Micrococcus lysodeikticus. Condensation of (XXXVI) with L-alanyl-D-isoglutamine benzyl ester (XIV), by means of N-ethyl-5-phenylisoxazolium-3'-sulfonate (NEPIS, Woodward's reagent K) as the coupling reagent, furnished amide (XLIX). The benzyl ester group of (XLIX) was finally cleaved by hydrogenolysis over Pd/C.
| 【1】 Vosika, G.J.; Cornelius, D.A.; Bennek, J.A.; Swenson, K.E.; Gilbert, C.W. (DOR BioPharma, Inc.); Compsn. for macrophage activation. US 5416070; WO 9116347 . |
| 【2】 Vosika, G.J.; Ma, F. (DOR BioPharma, Inc.); Preparation of glucosaminyl muramic acid derivs.. WO 9712894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 27130 | benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate | C15H21N3O4 | 详情 | 详情 | |
| (XXXVI) | 56354 | 2,3,4,5,6-pentafluorophenyl (2R)-2-{[(3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoate | C25H31F5N2O13 | 详情 | 详情 | |
| (XLIX) | 56366 | benzyl (4R)-4-({(2S)-2-[((2R)-2-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoyl)amino]propanoyl}amino)-5-amino-5-oxopentanoate | C34H51N5O16 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXXVI)The precursor N-acetylglucosaminyl-N-acetylmuramic acid (XXXVI) was obtained by an alternative route. The protected glucosamine acid (L) was esterified with benzyl alcohol in the presence of EDC and DMAP to yield the benzyl ester (LI). The 4,6-O-benzylidene group of (LI) was then subjected to reductive cleavage with NaBH3CN, producing the 6-O-benzyl-4-hydroxy derivative (LII). Coupling of (LII) with the thioglucoside (LIII) was accomplished in the presence of nitrosyl tetrafluoroborate, to afford (LIV). Depththaloylation and hydrolysis of (LIV) with methanolic butylamine provided (LV). Then, amino group acetylation with Ac2O in MeOH gave amide (LVI). The O-benzyl protecting groups of (LVI) were then removed by catalytic hydrogenation, leading to precursor (XXXVI).
| 【1】 Vosika, G.J.; Cornelius, D.A.; Bennek, J.A.; Swenson, K.E.; Gilbert, C.W. (DOR BioPharma, Inc.); Compsn. for macrophage activation. US 5416070; WO 9116347 . |
| 【2】 Vosika, G.J.; Ma, F. (DOR BioPharma, Inc.); Preparation of glucosaminyl muramic acid derivs.. WO 9712894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVI) | 56354 | 2,3,4,5,6-pentafluorophenyl (2R)-2-{[(3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoate | C25H31F5N2O13 | 详情 | 详情 | |
| (L) | 56367 | (2R)-2-{[(4aR,6S,7R,8R,8aS)-7-(acetylamino)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy}propanoic acid | C25H29NO8 | 详情 | 详情 | |
| (LI) | 56368 | benzyl (2R)-2-{[(4aR,6S,7R,8R,8aS)-7-(acetylamino)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy}propanoate | C32H35NO8 | 详情 | 详情 | |
| (LII) | 56369 | benzyl (2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-2-(benzyloxy)-6-[(benzyloxy)methyl]-5-hydroxytetrahydro-2H-pyran-4-yl}oxy)propanoate | C32H37NO8 | 详情 | 详情 | |
| (LIII) | 56370 | (2R,3S,4R,5R,6R)-3-(acetyloxy)-2-[(acetyloxy)methyl]-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6-(methylsulfanyl)tetrahydro-2H-pyran-4-yl acetate | C21H23NO9S | 详情 | 详情 | |
| (LIV) | 56371 | benzyl (2R)-2-[((2S,3R,4R,5S,6R)-3-(acetylamino)-2-(benzyloxy)-6-[(benzyloxy)methyl]-5-{[(2R,3R,4R,5R,6R)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-2-yl]oxy}tetrahydro-2H-pyran-4-yl)oxy]propanoate | C52H56N2O17 | 详情 | 详情 | |
| (LV) | 56372 | benzyl (2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoate | C38H48N2O12 | 详情 | 详情 | |
| (LVI) | 56373 | benzyl (2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoate | C40H50N2O13 | 详情 | 详情 |