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【结 构 式】 
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【分子编号】42056 【品名】tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-22-(cyanomethyl)-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoct 【CA登记号】 |
【 分 子 式 】C78H104Cl2N8O19Si2 【 分 子 量 】1584.80268 【元素组成】C 59.12% H 6.61% Cl 4.47% N 7.07% O 19.18% Si 3.54% |
合成路线1
该中间体在本合成路线中的序号：(XVI)The cyclization of (XII) by means of CsF in DMSO gives the tris macrocyclic compound (XIII), which is reduced at the NO2 group with H2 over Pd/C, yielding the amino derivative (XIV). The diazotation of (XIV) with t-Bu-ONO and HBF4, followed by reaction with CuCl2/CuCl, affords the corresponding chloro derivative (XV), which is silylated with Tbdms-N(Me)-COCF3 to provide the bis silyl ether (XVI).
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XIII) | 42053 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-5-chloro-22-(cyanomethyl)-2,18-dihydroxy-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-15-nitro-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2(3,6). | C66H76ClN9O21 | 详情 | 详情 | |
| (XIV) | 42054 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-15-amino-5-chloro-22-(cyanomethyl)-2,18-dihydroxy-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2(3,6). | C66H78ClN9O19 | 详情 | 详情 | |
| (XV) | 42055 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-5,15-dichloro-22-(cyanomethyl)-2,18-dihydroxy-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2(3,6).2(14 | C66H76Cl2N8O19 | 详情 | 详情 | |
| (XVI) | 42056 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-22-(cyanomethyl)-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoct | C78H104Cl2N8O19Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)Elimination of the Mem protecting group of (XVI) by treatment with borane (XVII) gives the primary alcohol (XVIII), which is oxidated to the corresponding acid with DMP and NaClO2 and simultaneously methylated with Tms-CHN2 to yield the methyl ester (XIX). The controlled hydrolysis of the cyano group of (XIX) with H2O2 and K2CO3 affords the corresponding amide (XX), which is finally desilylated with TBAF and demethylated with AlBr3 to furnish the target aglycon.
| 【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 |
|---|---|---|---|---|---|---|
| (XVI) | 42056 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-22-(cyanomethyl)-32,35,37,50-tetramethoxy-40-[[(2-methoxyethoxy)methoxy]methyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoct | C78H104Cl2N8O19Si2 | 详情 | 详情 | |
| (XVII) | 42057 | 2-Bromo-1,3,2-benzodioxaborole; B-Bromocatecholborane | 51901-85-0 | C6H4BBrO2 | 详情 | 详情 |
| (XVIII) | 42058 | tert-butyl (1R)-1-([[(1S,2R,18R,19R,22S,25R,28R,40S)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-22-(cyanomethyl)-40-(hydroxymethyl)-32,35,37,50-tetramethoxy-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2(3, | C74H96Cl2N8O17Si2 | 详情 | 详情 | |
| (XIX) | 42059 | methyl (1S,2R,18R,19R,22S,25R,28R,40S)-19-([(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoyl]amino)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-22-(cyanomethyl)-32,35,37,50-tetramethoxy-20,23,26,42,44-pentaoxo-7,13-dioxa-21,2 | C75H96Cl2N8O18Si2 | 详情 | 详情 | |
| (XX) | 42060 | methyl (1S,2R,18R,19R,22S,25R,28R,40S)-22-(2-amino-2-oxoethyl)-19-([(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoyl]amino)-2,18-bis[[tert-butyl(dimethyl)silyl]oxy]-5,15-dichloro-32,35,37,50-tetramethoxy-20,23,26,42,44-pentaoxo-7,13-dio | C75H98Cl2N8O19Si2 | 详情 | 详情 |