(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[([1-[(2R)-2-amino-3-methylbutanoyl]-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 -Drug Synthesis Database

【结构式】

【分子编号】49385

【品名】(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[([1-[(2R)-2-amino-3-methylbutanoyl]-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

【CA登记号】

【分子式】C₆₉H₁₀₀ClN₉O₁₄

【分子量】1315.05796

【元素组成】C 63.02% H 7.66% Cl 2.7% N 9.59% O 17.03%

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：(XV)

The anchoring of Fmoc-D-Val-OH (I) to Cl-TrtCl-RESIN (II) by means of DIEA, followed by cleavage of the Fmoc protecting group with piperidine in DMF, gives the resin-bonded valine (III), which is submitted to successive deprotection/coupling cycles with Fmoc-D-allo-Ile-OH (IV), Fmoc-D-allo-Thr-OH (VI) and again Fmoc-D-allo-Ile-OH (IV) to yield peptide resins (V), (VII) and (VIII), respectively. The coupling of Alloc-L-Val-OH (IX) to the free OH group of the Thr amino acid of peptide resin (VII) by means of DIPCDI and DMAP affords peptide resin (X), which is submitted to successive deprotection/coupling cycles with Fmoc-L-Orn(Boc)-OH (XI), Fmoc-D-Pro-OH (XIII) and Fmoc-D-Val-OH (I) to provide peptide resins (XII), (XIV) and (XV), 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	CAS号	分子式	供应商	用于合成
(I)	43354	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(III)	49374	(2-chlorophenyl)(diphenyl)methyl (2R)-2-amino-3-methylbutanoate		C₂₄H₂₄ClNO₂	详情	详情
(IV)	49375	(2R,3S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylpentanoic acid		C₂₁H₂₃NO₄	详情	详情
(V)	49376	(2-chlorophenyl)(diphenyl)methyl (2R)-2-[[(2R,3S)-2-amino-3-methylpentanoyl]amino]-3-methylbutanoate		C₃₀H₃₅ClN₂O₃	详情	详情
(VI)	49377	(2R,3R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-hydroxybutyric acid		C₁₉H₁₉NO₅	详情	详情
(VII)	49378	(2-chlorophenyl)(diphenyl)methyl (2R)-2-[((2R,3S)-2-[[(2R,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylpentanoyl)amino]-3-methylbutanoate		C₃₄H₄₂ClN₃O₅	详情	详情
(VIII)	49379	(2-chlorophenyl)(diphenyl)methyl (5R,8R,11R,14R)-1-(9H-fluoren-9-yl)-8-[(1R)-1-hydroxyethyl]-14-isopropyl-5,11-bis[(1S)-1-methylpropyl]-3,6,9,12-tetraoxo-2-oxa-4,7,10,13-tetraazapentadecan-15-oate		C₅₅H₆₃ClN₄O₈	详情	详情
(IX)	49380	(2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutyric acid		C₉H₁₅NO₄	详情	详情
(X)	49381	(2-chlorophenyl)(diphenyl)methyl (2R,5R,8R,9R,12S)-8-[[(2R,3S)-2-amino-3-methylpentanoyl]amino]-2,12-diisopropyl-9-methyl-5-[(1S)-1-methylpropyl]-4,7,11,14-tetraoxo-10,15-dioxa-3,6,13-triaza-17-octadecen-1-oate		C₄₉H₆₆ClN₅O₉	详情	详情
(XI)	49382	(2S)-5-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoic acid		C₂₅H₃₀N₂O₆	详情	详情
(XII)	49383	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-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-pentaazadoc		C₅₉H₈₄ClN₇O₁₂	详情	详情
(XIII)	34762	(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid	71989-31-6	C₂₀H₁₉NO₄	详情	详情
(XIV)	49384	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-9-[(2-pyrrolidinylcarbonyl)amino]-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate		C₆₄H₉₁ClN₈O₁₃	详情	详情
(XV)	49385	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[([1-[(2R)-2-amino-3-methylbutanoyl]-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		C₆₉H₁₀₀ClN₉O₁₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Successive deprotection/coupling cycles of peptide resin (XV) with Fmoc-L-Val-OH (XVI), Fmoc-L-Thr(tBu)-OH (XVIII), Fmoc-D-Val-OH (I) and 5-methylhexanoic acid (XXI) give peptide resins (XVII), (XIX), (XX) and (XXII), 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	CAS号	分子式	供应商	用于合成
(I)	43354	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(XV)	49385	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[([1-[(2R)-2-amino-3-methylbutanoyl]-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		C₆₉H₁₀₀ClN₉O₁₄	详情	详情
(XVI)	19932	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(XVII)	49386	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-([[1-((2R)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl)-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		C₇₄H₁₀₉ClN₁₀O₁₅	详情	详情
(XVIII)	18847	(2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid		C₂₃H₂₇NO₅	详情	详情
(XIX)	49387	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[[(1-[(2R)-2-[((2S)-2-[[(2S)-2-amino-3-(tert-butoxy)butanoyl]amino]-3-methylbutanoyl)amino]-3-methylbutanoyl]-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		C₈₂H₁₂₄ClN₁₁O₁₇	详情	详情
(XX)	49388			C₈₇H₁₃₃ClN₁₂O₁₈	详情	详情
(XXI)	27649	5-methylhexanoic acid	628-46-6	C₇H₁₄O₂	详情	详情
(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

Extended Information