　 -Drug Synthesis Database

【结构式】

【分子编号】40572

【品名】　

【CA登记号】

【分子式】C₈₃H₉₀ClFN₈O₂₄

【分子量】1638.1182232

【元素组成】C 60.86% H 5.54% Cl 2.16% F 1.16% N 6.84% O 23.44%

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：(XXII)

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).

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 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	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)

The cyclization of (XXII) by means of CsF in DMSO gives the tris macrocyclic compound (XXIII), which simultaneously eliminates the TEOC protecting group yielding (XXIV) with a free amino group. The silylation of the OH group of (XXIV) with CF3CO-N(Me)-TBDMS (B) affords the silyl ether (XXV), which is protected at its amino group with Troc-Cl (C) providing the fully protected compound (XXVI).

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 teicoplanin aglycon. J Am Chem Soc 2000, 122, 30, 7416.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	40575	N-[tert-butyl(dimethyl)silyl]-2,2,2-trifluoro-N-methylacetamide	77377-52-7	C₉H₁₈F₃NOSi	详情	详情
(XXII)	40572			C₈₃H₉₀ClFN₈O₂₄	详情	详情
(XXIII)	40573			C₈₃H₈₉ClN₈O₂₄	详情	详情
(XXIV)	40574			C₈₀H₈₅ClN₈O₂₃	详情	详情
(XXV)	40576			C₈₆H₉₉ClN₈O₂₃Si	详情	详情
(XXVI)	40577			C₈₉H₁₀₀Cl₄N₈O₂₅Si	详情	详情
(C)	13664	1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate	17341-93-4	C₃H₂Cl₄O₂	详情	详情

Extended Information