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【结 构 式】 
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【分子编号】47049 【品名】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 【CA登记号】 |
【 分 子 式 】C73H77ClN8O21 【 分 子 量 】1437.9084 【元素组成】C 60.98% H 5.4% Cl 2.47% N 7.79% O 23.37% |
合成路线1
该中间体在本合成路线中的序号：(XXV)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2
该中间体在本合成路线中的序号：(XXV)The reaction of the amino group of (XXV) with tBu-ONO, BHF4 and CuCl/CuCl2 gives the expected chloro derivative (XXVI), which is silylated at the OH group with CF3CON(Me)-Tbdms, yielding the silyl ether (XXVII). Elimination of the Mem protecting group of (XXVII) with the bromoboronate (XXVIII) affords the carbinol (XXIX), which is oxidized with DMP and NaClO2 to the corresponding carboxylic acid (XXX).
| 【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (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 | |
| (XXVI) | 47050 | tert-butyl (1S,2R,19R,22R,34S,37R,40R,52S)-5,15-dichloro-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 | C73H75Cl2N7O21 | 详情 | 详情 | |
| (XXVII) | 40582 | C79H89Cl2N7O21Si | 详情 | 详情 | ||
| (XXVIII) | 42057 | 2-Bromo-1,3,2-benzodioxaborole; B-Bromocatecholborane | 51901-85-0 | C6H4BBrO2 | 详情 | 详情 |
| (XXIX) | 40583 | C75H81Cl2N7O19Si | 详情 | 详情 | ||
| (XXX) | 40584 | C75H79Cl2N7O20Si | 详情 | 详情 |