　 -Drug Synthesis Database

【结构式】

【分子编号】49394

【品名】　

【CA登记号】

【分子式】C₁₀₇H₁₆₀ClN₁₃O₂₃

【分子量】2031.97392

【元素组成】C 63.25% H 7.94% Cl 1.74% N 8.96% O 18.11%

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：(XXVII)

Elimination of the Alloc protecting group of resin (XXII) by means of Pd(PPh3)4 and PhSiH3 gives peptide resin (XXIII), which is coupled successively with Fmoc-L-Thr-OH (XXIV) and Alloc-L-Phe-OH (XXVI) to yield peptide resins (XXV) and (XXVII), respectively.

参考文献中间体

合成目标

【1】 Royo, M.; Manzanares, I.; Lopez, A.; Jimenez, J.C.; Albericio, F.; Giralt, E.; Rodrigues, I. (PharmaMar, SA); Kahalalide cpds.. WO 0158934 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXII)	49389	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate	C₉₄H₁₄₅ClN₁₂O₁₉	详情	详情
(XXIII)	49390	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-((1R)-1-[[(2S)-2-amino-3-methylbutanoyl]oxy]ethyl)-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate	C₉₀H₁₄₁ClN₁₂O₁₇	详情	详情
(XXIV)	49391	(2S,3R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-hydroxybutyric acid	C₁₉H₁₉NO₅	详情	详情
(XXV)	49392	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]oxy]-3-methylbutanoyl)oxy]ethyl]-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate	C₉₄H₁₄₇ClN₁₂O₂₀	详情	详情
(XXVI)	49393	(2S)-2-[[(allyloxy)carbonyl]amino]-3-phenylpropionic acid	C₁₃H₁₅NO₄	详情	详情
(XXVII)	49394		C₁₀₇H₁₆₀ClN₁₃O₂₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVII)

The dehydration of peptide resin (XXVII) by means of EDC and CuCl in DMF/dichloromethane, followed by elimination of the Alloc protecting group with Pd(PPh3)4 and PhSiH3, gives the peptide resin (XXVIII). The cleavage of the protected peptide from the resin was performed with TFA in dichloromethane to yield peptide (XXIX), which is cyclized by means of DIEA and benzotriazol-1-yl-N-oxy-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP) and finally deprotected with TFA in water to afford the target kahalalide F.

参考文献中间体

合成目标

【1】 Royo, M.; Manzanares, I.; Lopez, A.; Jimenez, J.C.; Albericio, F.; Giralt, E.; Rodrigues, I. (PharmaMar, SA); Kahalalide cpds.. WO 0158934 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXVII)	49394		C₁₀₇H₁₆₀ClN₁₃O₂₃	详情	详情
(XXVIII)	49395	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-([(2S)-2-[((Z)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-2-butenoyl)oxy]-3-methylbutanoyl]oxy)ethyl]-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate	C₁₀₃H₁₅₄ClN₁₃O₂₀	详情	详情
(XXIX)	49396	(9S,12R,15R,18R,21R)-15-[(1R)-1-([(2S)-2-[((Z)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-2-butenoyl)oxy]-3-methylbutanoyl]oxy)ethyl]-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oic acid	C₈₄H₁₄₁N₁₃O₂₀	详情	详情

Extended Information