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【结 构 式】

【分子编号】40567

【品名】methyl (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.; methyl (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.; methyl (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.

【CA登记号】

【 分 子 式 】C55H63ClN4O18

【 分 子 量 】1103.57408

【元素组成】C 59.86% H 5.75% Cl 3.21% N 5.08% O 26.1%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XVII)

The cyclization of tripeptide derivative (XII) (assembled n three steps from the corresponding amino acids) by means of K2CO3/CaCO3 gives the macrocyclic peptide (XIII), which was reduced at its NO2 group with H2 over Pd/C and treated with tert-butyl nitrite, HBF4 and CuCl2 to obtain the corresponding chloro derivative (XIV). The condensation of (XIV) with the boronic acid derivative (XV) by means of a Pd catalyst affords the biphenyl derivative (XVI), which is desilylated with Bu4NF giving the secondary alcohol (XVII). The hydrolysis of the methyl ester of (XVII) with LiOH yields the corresponding carboxylic acid (XVIII).

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 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) 40562 methyl (6R,9R)-9-(3-bromo-4-methylphenyl)-12-[(R)-[[tert-butyl(dimethyl)silyl]oxy](4-fluoro-3-nitrophenyl)methyl]-6-(3,5-dihydroxy-4-methylphenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate C39H50BrFN4O12Si 详情 详情
(XIII) 40563 methyl (8R,11R,14S,15R)-11-(3-bromo-4-methylphenyl)-8-[(tert-butoxycarbonyl)amino]-15-[[tert-butyl(dimethyl)silyl]oxy]-4,5-dihydroxy-18-nitro-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21),4,6,16,19-hexaene-14-carboxylate C39H49BrN4O12Si 详情 详情
(XIV) 40564 methyl (8R,11R,14S,15R)-11-(3-bromo-4-methylphenyl)-8-[(tert-butoxycarbonyl)amino]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-4,5-dihydroxy-9,12-dioxo-2-oxa-10,13-diazatricyclo[14.2.2.1(3,7)]henicosa-1(18),3(21),4,6,16,19-hexaene-14-carboxylate C39H49BrClN3O10Si 详情 详情
(XV) 40565 2-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4,6-dimethylphenylboronic acid C22H30BNO7 详情 详情
(XVI) 40566 methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox; methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox; methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox C61H77ClN4O18Si 详情 详情
(XVII) 40567 methyl (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.; methyl (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.; methyl (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. C55H63ClN4O18 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

合成路线2

该中间体在本合成路线中的序号:(VI)

The cyclization of tripeptide derivative (I) (assembled in three steps from the corresponding amino acids) by means of K2CO3/CaCO3 gives the macrocyclic peptide (II), which was reduced at its NO2 group with H2 over Pd/C and treated with tert-butyl nitrite, HBF4 and CuCl2 to obtain the corresponding chloro derivative (III). The condensation of (III) with the boronic acid derivative (IV) by means of a Pd catalyst affords the biphenyl derivative (V), which is desilylated with Bu4NF, giving the secondary alcohol (VI). The hydrolysis of the methyl ester of (VI) with LiOH yields the corresponding carboxylic acid (VII).

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
(I) 42041 methyl (6R,9R)-9-(3-bromo-4-methoxyphenyl)-12-[(R)-[[tert-butyl(dimethyl)silyl]oxy](4-fluoro-3-nitrophenyl)methyl]-6-(3,5-dihydroxy-4-methoxyphenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate C39H50BrFN4O13Si 详情 详情
(II) 42042   C39H49BrN4O13Si 详情 详情
(III) 42043   C39H49BrClN3O11Si 详情 详情
(IV) 42044 2-[(1S)-1-[[(benzyloxy)carbonyl]amino]-2-[(2-methoxyethoxy)methoxy]ethyl]-4,6-dimethoxyphenylboronic acid C22H30BNO9 详情 详情
(V) 40566 methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox; methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox; methyl (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]-15-[[tert-butyl(dimethyl)silyl]oxy]-18-chloro-5-hydroxy-4-methoxy-9,12-diox C61H77ClN4O18Si 详情 详情
(VI) 40567 methyl (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.; methyl (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.; methyl (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. C55H63ClN4O18 详情 详情
(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
Extended Information