1-(9H-fluoren-9-yl)-9,16-dimethyl-12,20-bis[(methyloxy)carbonyl]-3,6,10,15,18-pentaoxo-8-(2-phenylethenyl)-5-(phenylmethyl)-2-oxa-4,7,11,16,19-pentaazadocosan-22-oic acid -Drug Synthesis Database

【结构式】

【分子编号】52449

【品名】1-(9H-fluoren-9-yl)-9,16-dimethyl-12,20-bis[(methyloxy)carbonyl]-3,6,10,15,18-pentaoxo-8-(2-phenylethenyl)-5-(phenylmethyl)-2-oxa-4,7,11,16,19-pentaazadocosan-22-oic acid

【CA登记号】

【分子式】C₅₀H₅₅N₅O₁₂

【分子量】918.0132

【元素组成】C 65.42% H 6.04% N 7.63% O 20.91%

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：(XXIII)

The deprotection of Wang-RESIN-coupled N-Fmoc-D-aspartic acid alpha-methyl ester (XII) with piperidine in DMF gives the free RESIN-coupled aspartic acid monoester (XIII), which is condensed with N-Fmoc-sarcosine (XIV) by means of PyBOP in DMF to yield the dipeptide (XV). Deprotection with piperidine affords (XVI), and coupling with PyBOP was repeated with the L-glutamate (XVII) to afford tripeptide (XVIII); with deprotected (XIX) and the intermediate amino acid (XI) to provide tetrapeptide (XX); and with deprotected (XXI) and -Fmoc-L-phenylalanine (XXII) to furnish finally the protected RESIN-bounded pentapeptide (XXIII).

参考文献中间体

合成目标

【1】 O'Donnell, M.E.; et al.; Serine-threonine protein phosphatase inhibitors derived from nodularin: Role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint. J Chem Soc - Perkins Trans I 2001, 14, 1696.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	52438	3-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-2-methyl-5-phenyl-4-pentenoic acid		C₂₇H₂₅NO₄	详情	详情
(XII)	52439	3-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₀H₁₉NO₆	详情	详情
(XIII)	52440	3-amino-4-(methyloxy)-4-oxobutanoic acid		C₅H₉NO₄	详情	详情
(XIV)	52441	2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetic acid		C₁₈H₁₇NO₄	详情	详情
(XV)	52442	3-({2-[{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}(methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₃H₂₄N₂O₇	详情	详情
(XVI)	52443	3-{[2-(methylamino)acetyl]amino}-4-(methyloxy)-4-oxobutanoic acid		C₈H₁₄N₂O₅	详情	详情
(XVII)	52444	4-({[(9H-fluoren-9-ylmethyl)oxy]carbonyl}amino)-5-(methyloxy)-5-oxopentanoic acid		C₂₁H₂₁NO₆	详情	详情
(XVIII)	52445	1-(9H-fluoren-9-yl)-9-methyl-5,13-bis[(methyloxy)carbonyl]-3,8,11-trioxo-2-oxa-4,9,12-triazapentadecan-15-oic acid		C₂₉H₃₃N₃O₁₀	详情	详情
(XIX)	52446	3-({2-[[4-amino-5-(methyloxy)-5-oxopentanoyl](methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₁₄H₂₃N₃O₈	详情	详情
(XX)	52447	1-(9H-fluoren-9-yl)-6,13-dimethyl-9,17-bis[(methyloxy)carbonyl]-3,7,12,15-tetraoxo-5-(2-phenylethenyl)-2-oxa-4,8,13,16-tetraazanonadecan-19-oic acid		C₄₁H₄₆N₄O₁₁	详情	详情
(XXI)	52448	3-({2-[[4-[(3-amino-2-methyl-5-phenyl-4-pentenoyl)amino]-5-(methyloxy)-5-oxopentanoyl](methyl)amino]acetyl}amino)-4-(methyloxy)-4-oxobutanoic acid		C₂₆H₃₆N₄O₉	详情	详情
(XXII)	19030	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid; N-((9H-fluoren-9-ylmethoxy)carbonyl)-phenylalanine	35661-40-6	C₂₄H₂₁NO₄	详情	详情
(XXIII)	52449	1-(9H-fluoren-9-yl)-9,16-dimethyl-12,20-bis[(methyloxy)carbonyl]-3,6,10,15,18-pentaoxo-8-(2-phenylethenyl)-5-(phenylmethyl)-2-oxa-4,7,11,16,19-pentaazadocosan-22-oic acid		C₅₀H₅₅N₅O₁₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXIII)

The reaction of (XXIII) with piperidine deprotects the terminal NH2 group, and treatment with TFA cleaves the resin bond, leaving the free pentapeptide (XXIV). The cyclization of (XXIV) by means of BOP-Cl and DIEA in DMF/dichloromethane gives the cyclic pentapeptide dimethyl ester (XXV), which is finally hydrolyzed with LiOH in THF/water to afford the target cyclic pentapeptide.

参考文献中间体

合成目标

【1】 O'Donnell, M.E.; et al.; Serine-threonine protein phosphatase inhibitors derived from nodularin: Role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint. J Chem Soc - Perkins Trans I 2001, 14, 1696.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIII)	52449	1-(9H-fluoren-9-yl)-9,16-dimethyl-12,20-bis[(methyloxy)carbonyl]-3,6,10,15,18-pentaoxo-8-(2-phenylethenyl)-5-(phenylmethyl)-2-oxa-4,7,11,16,19-pentaazadocosan-22-oic acid	C₅₀H₅₅N₅O₁₂	详情	详情
(XXIV)	52450	18-amino-7,14-dimethyl-3,11-bis[(methyloxy)carbonyl]-5,8,13,17-tetraoxo-19-phenyl-15-(2-phenylethenyl)-4,7,12,16-tetraazanonadecan-1-oic acid	C₃₅H₄₅N₅O₁₀	详情	详情
(XXV)	52451	dimethyl 1,13-dimethyl-3,7,10,14,19-pentaoxo-12-(2-phenylethenyl)-9-(phenylmethyl)-1,4,8,11,15-pentaazacyclononadecane-5,16-dicarboxylate	C₃₅H₄₃N₅O₉	详情	详情

Extended Information