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【结 构 式】 
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【分子编号】40571 【品名】(1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca 【CA登记号】 |
【 分 子 式 】C41H45ClN4O13 【 分 子 量 】837.28016 【元素组成】C 58.82% H 5.42% Cl 4.23% N 6.69% O 24.84% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号：(XXI)Selective deprotection of the benzyloxycarbonylamino group of (XVIII) with H2 over Pd/C gives the corresponding amino derivative (XIX), which is cyclized by means of EDC and HOBT yielding the bicyclic peptide (XX). Elimination of the Boc protecting group of (XX) with formic acid affords the primary amine (XXI), which is acylated with the previously obtained dipeptide intermediate (XI) by means of DEPBT providing the adduct (XXII).
| 【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862. |
| 【2】 Boger, D.L.; et al.; Total synthesis of the teicoplanin aglycon. J Am Chem Soc 2000, 122, 30, 7416. |
| 【3】 Boger, D.L.; et al.; Total synthesis of the vancomycin aglycon. J Am Chem Soc 1999, 121, 43, 10004. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 40561 | (2S)-2-[3-(5-[(1R)-2-(benzyloxy)-1-[(tert-butoxycarbonyl)amino]ethyl]-2-methoxyphenoxy)-5-methoxyphenyl]-2-[[(2R)-3-(4-fluoro-3-nitrophenyl)-2-(propionylamino)propanoyl]amino]ethanoic acid | C42H47FN4O12 | 详情 | 详情 | |
| (XVIII) | 40568 | (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3; (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3; (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3 | C54H61ClN4O18 | 详情 | 详情 | |
| (XIX) | 40569 | (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21; (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21; (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21 | C46H55ClN4O16 | 详情 | 详情 | |
| (XX) | 40570 | tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3; tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3; tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3 | C46H53ClN4O15 | 详情 | 详情 | |
| (XXI) | 40571 | (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca | C41H45ClN4O13 | 详情 | 详情 | |
| (XXII) | 40572 | C83H90ClFN8O24 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXII)Assembly of the target compound: The condensation of the carboxylic acid intermediate (XXI) with the free amino group of the intermediate cyclopeptide (XXII) by means of DEPBT gives the corresponding amide (XXIII), which is cyclized by means of CsF in DMSO yielding the macrocyclic ether (XXIV). The reduction of the nitro group of (XXIV) with H2 over Pd/C affords the corresponding amino derivative (XXV).
| 【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862. |
| 【2】 Boger, D.L.; et al.; Total synthesis of the teicoplanin aglycon. J Am Chem Soc 2000, 122, 30, 7416. |
| 【3】 Johnson, T.A.; et al.; Highly diastereoselective and enantioselective carbon- -carbon bond formations in conjugate additions of lithiated N-boc allylamines to nitroalkenes: Enantioselective synthesis of 3,4- and 3,4,5-substituted piperidines including (-)-paroxetine. J Am Chem Soc 2001, 123, 5, 1004. |
| 【4】 Boger, D.L.; et al.; Diasteroselective total synthesis of the vancomycin aglycon with ordered atropisomer equilibrations. J Am Chem Soc 1999, 121, 13, 3226. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 47046 | (8S,11R,14R)-14-[(tert-butoxycarbonyl)amino]-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaene-8-carboxylic acid | C32H33FN4O11 | 详情 | 详情 | |
| (XXII) | 40571 | (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca | C41H45ClN4O13 | 详情 | 详情 | |
| (XXIII) | 47047 | tert-butyl (8S,11R,14R)-8-([[(1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodecaen-28-yl]amino]carbonyl)-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaen-14-ylcarbamate | C73H76ClFN8O23 | 详情 | 详情 | |
| (XXIV) | 47048 | tert-butyl (1S,2R,19R,22R,34S,37R,40R,52S)-5-chloro-2-hydroxy-26,31,44,47,49,66-hexamethoxy-52-(((2-methoxyethoxy)methoxy)methyl)-15-nitro-21,35,38,54,56,58-hexaoxo-7,13,28-trioxa-20,36,39,53,55,57-hexaazaundecacyclo[38.14.2.2(3,6).2(14,17).2(19,34).1(8,12).1(23,27).1(29,33).1(41,45).0(10,37).0(46,51)]hexahexaconta-3,5,8(66),9,11,14,16,23(65),24,26,29(carbamate | C73H75ClN8O23 | 详情 | 详情 | |
| (XXV) | 47049 | tert-butyl (1S,2R,19R,22R,34S,37R,40R,52S)-15-amino-5-chloro-2-hydroxy-26,31,44,47,49,66-hexamethoxy-52-(((2-methoxyethoxy)methoxy)methyl)-21,35,38,54,56,58-hexaoxo-7,13,28-trioxa-20,36,39,53,55,57-hexaazaundecacyclo[38.14.2.2(3,6).2(14,17).2(19,34).1(8,12).1(23,27).1(29,33).1(41,45).0(10,37).0(46,51)]hexahexaconta-3,5,8(66),9,11,14,16,23(65),24,26,29(carbamate | C73H77ClN8O21 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(X)Selective deprotection of the benzyloxycarbonylamino group of (VII) with H2 over Pd/C gives the corresponding amino derivative (VIII), which is cyclized by means of EDC and HOBT, yielding the bicyclic peptide (IX). Elimination of the Boc protecting group of (IX) with formic acid affords the primary amine (X) , which is acylated with the tripeptide intermediate (XI) by means of EDC and HOAt, providing the adduct (XII).
| 【1】 Boger, D.L.; et al.; Diasteroselective total synthesis of the vancomycin aglycon with ordered atropisomer equilibrations. J Am Chem Soc 1999, 121, 13, 3226. |
| 【2】 Boger, D.L.; et al.; Total synthesis of the vancomycin aglycon. J Am Chem Soc 1999, 121, 43, 10004. |
| 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) | 40568 | (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3; (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3; (8R,11R,14S,15R)-11-(2'-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3 | C54H61ClN4O18 | 详情 | 详情 | |
| (VIII) | 40569 | (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21; (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21; (8R,11R,14S,15R)-11-(2'-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-4',6,6'-trimethoxy[1,1'-biphenyl]-3-yl)-8-[(tert-butoxycarbonyl)amino]-18-chloro-5,15-dihydroxy-4-methoxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21 | C46H55ClN4O16 | 详情 | 详情 | |
| (IX) | 40570 | tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3; tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3; tert-butyl (1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(3 | C46H53ClN4O15 | 详情 | 详情 | |
| (X) | 40571 | (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca; (1R,13S,16S,17R,28R)-28-amino-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriaconta-2(36),3,5,7,9,11,18,20,23(35),24,26,33-dodeca | C41H45ClN4O13 | 详情 | 详情 | |
| (XI) | 42051 | (6R,9R,12S)-12-(cyanomethyl)-9-[(R)-(4-fluoro-3-nitrophenyl)(hydroxy)methyl]-6-isobutyl-2,2,5-trimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid | C25H34FN5O9 | 详情 | 详情 | |
| (XII) | 42052 | tert-butyl (1R)-1-([[(1R,2R)-1-([[(1S)-2-[[(1R,13S,16S,17R,28R)-20-chloro-17,25-dihydroxy-5,8,10,24-tetramethoxy-13-[[(2-methoxyethoxy)methoxy]methyl]-15,29,31-trioxo-22-oxa-14,30,32-triazahexacyclo[14.14.2.2(18,21).1(2,6).1(23,27).0(7,12)]hexatriac | C66H77ClFN9O21 | 详情 | 详情 |
Extended Information