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 -Drug Synthesis Database

【结构式】

【分子编号】40566

【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]-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

【CA登记号】

【分子式】C₆₁H₇₇ClN₄O₁₈Si

【分子量】1217.83674

【元素组成】C 60.16% H 6.37% Cl 2.91% N 4.6% O 23.65% Si 2.31%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVI)

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).

参考文献中间体

合成目标

【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	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：(V)

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).

参考文献中间体

合成目标

【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	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