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【结 构 式】 
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【分子编号】25999 【品名】(3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid 【CA登记号】 |
【 分 子 式 】C83H88Cl2N8O29 【 分 子 量 】1732.55364 【元素组成】C 57.54% H 5.12% Cl 4.09% N 6.47% O 26.78% |
合成路线1
该中间体在本合成路线中的序号：(I)BI 397 is the 3-(dimethylamino)-1-propylamide at the peptide-carboxy group of the natural glycopeptide A-40,926. BI 397 is prepared from A-40,926 following a three-step procedure which consists of: 1) selective methyl esterification of the N-acylaminoglucuronic acid function, 2) amidation of the peptide-carboxy group and 3) saponification of the sugar methyl ester. Steps 2 and 3 are performed in one-pot. Step 1): Reaction of A-40,926 (A) (I) in methanol in the presence of H2SO4 at 0-5 C for 24 h gives the monomethyl ester (MA) (II) at the sugar-carboxy group (80% yield). Step 2): Amidation at the peptide-carboxy group is carried out by reaction of MA (II) with 3-(dimethylamino)-1-propylamine (DMEPA) (III) in DMSO in the presence of PyBOP to obtain the methyl ester (MA-A-1) (IV) of BI 397; this compound is not isolated. Step 3): Hydrolysis of MA-A-1 (IV) in the above DMSO solution with 15% NAOH gives BI 397 (A-A-1, 63% yield from MA).
| 【1】 Scotti, R.; Kurz, M.; Andreini, B.P.; Goldstein, B.P.; Denaro, M.; Ferrari, P.; Ciabatti, R.; Malabarba, A.; New semisynthetic glycopepetides MDL 63,246 and MDL 63,042, and other amide derivatives of antibiotic A-40,926 active against glycopeptide-resistant VanA enterococci. J Antibiot 1995, 48, 8, 869. |
| 【2】 Donadio, S.; Malabarba, A.; BI 397. Drugs Fut 1999, 24, 8, 839. |
| 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) | 25999 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid | C83H88Cl2N8O29 | 详情 | 详情 | |
| (II) | 26000 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid | C84H90Cl2N8O29 | 详情 | 详情 | |
| (III) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (IV) | 26001 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-N-[3-(dimethylamino)propyl]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxamide; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-N-[3-(dimethylamino)propyl]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclote | C89H102Cl2N10O28 | 详情 | 详情 |