• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】43354

【品名】(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid

【CA登记号】

【 分 子 式 】C20H21NO4

【 分 子 量 】339.39108

【元素组成】C 70.78% H 6.24% N 4.13% O 18.86%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(I)

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.

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:(I)

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.

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

合成路线3

该中间体在本合成路线中的序号:(XVII)

The Fmoc protecting group of resin (XI) was removed by treatment with piperidine in DMF to give (XII). This was subsequently coupled with N-Fmoc-3-methyl-L-valine (XIII) to provide, after Fmoc deprotection with piperidine, the dipeptide resin (XIV). Further coupling and deprotection cycles with N-Fmoc-3-(2-methylphenyl)-L-alanine (XV) and N-Fmoc-D-valine (XVII) yielded resins (XVI) and (XVIII), respectively. Resin (XVIII) was then coupled with N-(benzyloxycarbonyl)-L-aspartic acid beta-tert-butyl ester (XIX), and the title compound was finally deprotected and liberated from the resin by means of trifluoroacetic acid in CH2Cl2.

1 Dunsdon, R.M.; et al.; Solid phase synthesis of aminoboronic acids: Potent inhibitors of the hepatitis C virus NS3 proteinase. Bioorg Med Chem Lett 2000, 10, 14, 1577.
2 Attwood, M.R.; Hurst, D.N.; Jones, P.S.; Kay, P.B.; Raynham, T.M.; Wilson, F.X. (F. Hoffmann-La Roche AG); Antiviral peptide derivs.. JP 2000508344; WO 9822496 .
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) 43348 9H-fluoren-9-ylmethyl (1S)-1-[([1-[4-(5-amino-3-methyl-5-oxopentyl)-4,5,5-trimethyl-1,3,2-dioxaborolan-2-yl]propyl]amino)carbonyl]-3-methylbutylcarbamate C35H50BN3O6 详情 详情
(XII) 43349 (2S)-2-amino-N-[1-[4-(5-amino-3-methyl-5-oxopentyl)-4,5,5-trimethyl-1,3,2-dioxaborolan-2-yl]propyl]-4-methylpentanamide C20H40BN3O4 详情 详情
(XIII) 43350 (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3,3-dimethylbutyric acid 132684-60-7 C21H23NO4 详情 详情
(XIV) 43351 (2S)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-N-[1-[4-(5-amino-3-methyl-5-oxopentyl)-4,5,5-trimethyl-1,3,2-dioxaborolan-2-yl]propyl]-4-methylpentanamide C26H51BN4O5 详情 详情
(XV) 22255 (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-methylphenyl)propionic acid C25H23NO4 详情 详情
(XVI) 43352 (2S)-N-[1-[4-(5-amino-3-methyl-5-oxopentyl)-4,5,5-trimethyl-1,3,2-dioxaborolan-2-yl]propyl]-2-[((2S)-2-[[(2S)-2-amino-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-4-methylpentanamide C36H62BN5O6 详情 详情
(XVII) 43354 (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid C20H21NO4 详情 详情
(XVIII) 43353 (2S)-2-[((2S)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-N-[1-[4-(5-amino-3-methyl-5-oxopentyl)-4,5,5-trimethyl-1,3,2-dioxaborolan-2-yl]propyl]-4-methylpentanamide C41H71BN6O7 详情 详情
(XIX) 36564 (2S)-2-[[(benzyloxy)carbonyl]amino]-4-(tert-butoxy)-4-oxobutyric acid C16H21NO6 详情 详情
Extended Information