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【结 构 式】 
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【分子编号】18854 【品名】(2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid 【CA登记号】 |
【 分 子 式 】C26H32N2O6 【 分 子 量 】468.54996 【元素组成】C 66.65% H 6.88% N 5.98% O 20.49% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Compound (XI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin. After removal of Fmoc protecting group from the resin with 20% piperidine in N-methyl-2-pyrrolidinone (NMP), a coupling cycle was carried out with Fmoc-Thr(O-t-Bu)OH (I) using bromotripyrrolidino phosphonium hexafluorophosphate (PyBroP) and diisopropylethylamine (DIEA) in NMP, followed by Fmoc removal with 20% piperidine in NMP. To the Thr-bound resin (II) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc- (N-allyloxycarbonylpropyl)PheOH (IV), Fmoc-ValCl (VI), Fmoc-Lys(Boc)OH (VIII), and Fmoc-D-TrpOH (X) to yield the corresponding peptide-bound resins (V), (VII), (IX) and (XI), respectively.
| 【1】 Gilon, C.; et al.; A backbone-cyclic, receptor 5-selective somatostatin analogue: Synthesis, bioactivity, and nuclear magnetic resonance conformational analysis. J Med Chem 1998, 41, 6, 919. |
| 【2】 Hornik, V.; Seri-Levy, A.; Gellerman, G.; Gilon, C. (Yissum Research Development Co.); Conformationally constrained backbone cyclized somatostatin analogs. WO 9804583 . |
| 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) | 18847 | (2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid | C23H27NO5 | 详情 | 详情 | |
| (II) | 18848 | 9H-fluoren-9-ylmethyl (1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propylcarbamate | C23H28N2O4 | 详情 | 详情 | |
| (III) | 18849 | (2S,3R)-2-amino-3-(tert-butoxy)butanamide | C8H18N2O2 | 详情 | 详情 | |
| (IV) | 18850 | (2S)-2-[[4-(allyloxy)-4-oxobutyl][(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid | C31H31NO6 | 详情 | 详情 | |
| (V) | 18851 | allyl 4-[((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)amino]butanoate | C24H37N3O5 | 详情 | 详情 | |
| (VI) | 18852 | 9H-fluoren-9-ylmethyl (1S)-1-(chlorocarbonyl)-2-methylpropylcarbamate | 103321-53-5 | C20H20ClNO3 | 详情 | 详情 |
| (VII) | 18853 | allyl 4-[((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)[(2S)-2-amino-3-methylbutanoyl]amino]butanoate | C29H46N4O6 | 详情 | 详情 | |
| (VIII) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (IX) | 18855 | allyl (10S,13S)-10-amino-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate | C40H66N6O9 | 详情 | 详情 | |
| (X) | 18856 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(1H-indol-3-yl)propionic acid | C26H22N2O4 | 详情 | 详情 | |
| (XI) | 18857 | allyl (10S,13S)-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-10-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate | C51H76N8O10 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The compound was prepared by solid-phase peptide synthesis on a poliethylene glycol amino resin. Coupling with N(alpha)-Fmoc-N(G)-Boc-lysine (I) using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and N-methylmorpholine (NMM) afforded the protected lysine-linked resin (II), and subsequent Fmoc deprotection provided resin (III). This was submitted to further coupling and deprotection cycles with the N(alpha)-Fmoc-protected amino acids proline (IV), N(G)-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)arginine (VI), D-alanine (VIII), N(G)-Pbf-arginine (VI), and again N(G)-Pbf-arginine (VI) yielding peptide resins (V), (VII), (IX), (X) and (XI).
| 【1】 Aldrich, J.V.; Murray, T.F.; Wan, Q.; A novel acetylated analogue of dynorphin A-(1-11) amide as a kappa-opioid receptor antagonist. J Med Chem 1999, 42, 16, 3011. |
| 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) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (II) | 28723 | 9H-fluoren-9-ylmethyl (1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentylcarbamate | C26H33N3O5 | 详情 | 详情 | |
| (III) | 34761 | tert-butyl (5S)-5,6-diamino-6-oxohexylcarbamate | C11H23N3O3 | 详情 | 详情 | |
| (IV) | 34762 | (2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid | 71989-31-6 | C20H19NO4 | 详情 | 详情 |
| (V) | 34763 | tert-butyl (5S)-6-amino-6-oxo-5-[[(2S)pyrrolidinylcarbonyl]amino]hexylcarbamate | C16H30N4O4 | 详情 | 详情 | |
| (VI) | 34764 | (2S)-5-[[[[(9H-fluoren-9-ylmethoxy)carbonyl]amino](imino)methyl]amino]-2-[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]pentanoic acid | C34H40N4O7S | 详情 | 详情 | |
| (VII) | 34765 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-amino-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C35H58N8O8S | 详情 | 详情 | |
| (VIII) | 19926 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C18H17NO4 | 详情 | 详情 | |
| (IX) | 34766 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-[[(2R)-2-aminopropanoyl]amino]-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C38H63N9O9S | 详情 | 详情 | |
| (X) | 34767 | tert-butyl (5S)-6-amino-5-[[((2S)-1-[(2S)-2-[[(2R)-2-([(2S)-2-amino-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]amino)propanoyl]amino]-5-[(imino[[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino]methyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-6-oxohexylcarbamate | C57H91N13O13S2 | 详情 | 详情 | |
| (XI) | 34768 | tert-butyl (5S)-6-amino-5-({[(2S)-1-((2S,5R,8S,11S)-11-amino-16-imino-2,8-bis{3-[(imino{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}methyl)amino]propyl}-5-methyl-4,7,10-trioxo-16-{[(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}-3,6,9,15-tetraazahexadec-1-anoyl)pyrrolidinyl]carbonyl}amino)-6-oxohexylcarbamate | C76H119N17O17S3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Further coupling and deprotection cycles with N(epsilon)-Boc-lysine (I), and O-tert-butyl-tyrosine (XVIII), yielded the peptide resins (XVII) and (XIX), respectively. Then, acetylation of the free amino group of peptide resin (XIX) with Ac2O, and final deprotection and cleavage from the resin by means of moist trifluoroacetic acid, phenol and triisopropylsilane furnished the title peptide amide.
| 【1】 Aldrich, J.V.; Murray, T.F.; Wan, Q.; A novel acetylated analogue of dynorphin A-(1-11) amide as a kappa-opioid receptor antagonist. J Med Chem 1999, 42, 16, 3011. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23540 | Phenol | 108-95-2 | C6H6O | 详情 | 详情 | |
| (I) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (XVI) | 34772 | C114H166N22O24S3 | 详情 | 详情 | ||
| (XVII) | 34773 | C125H186N24O27S3 | 详情 | 详情 | ||
| (XVIII) | 34774 | (2S)-2-[tert-butyl[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid | C28H29NO5 | 详情 | 详情 | |
| (XIX) | 34775 | C138H203N25O29S3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The successive condensations of fluorenylmethoxycarbonyl-Rink amide resin (I) with Nalpha-FMOC-Nepsilon-Boc-L-lysine (II), FMOC-D-phenylalanine (IV), FMOC-D-2-naphthylalanine (VI), FMOC-Npi-trityl-L-histidine (VIII), and finally 2-(tert-butoxycarbonylamino)isobutyric acid (X), using the solid phase peptide technique synthesis yielded resins (III), (V), (VII), (IX) and finally (XI). This last resin was then treated with trifluoroacetic acid in order to eliminate the Boc protecting groups and the solid phase resin and isolate the target compound.
| 【1】 Muller, L.; et al.; C-14-labelling of ipamorelin, a growth hormone secretagogue. J Label Compd Radiopharm 1998, 41, 12, 1093. |
| 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) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (II) | 28722 | 9H-fluoren-9-ylmethyl carbamate | 84418-43-9 | C15H13NO2 | 详情 | 详情 |
| (III) | 28723 | 9H-fluoren-9-ylmethyl (1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentylcarbamate | C26H33N3O5 | 详情 | 详情 | |
| (IV) | 28730 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid | C24H21NO4 | 详情 | 详情 | |
| (V) | 28724 | 9H-fluoren-9-ylmethyl (1R)-2-([(1S)-1-(aminocarbonyl)-5-[(tert-butoxycarbonyl)amino]pentyl]amino)-1-benzyl-2-oxoethylcarbamate | C35H42N4O6 | 详情 | 详情 | |
| (VI) | 28725 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-naphthyl)propionic acid | C28H23NO4 | 详情 | 详情 | |
| (VII) | 28726 | 9H-fluoren-9-ylmethyl (1R,4R,7S)-7-(aminocarbonyl)-4-benzyl-15,15-dimethyl-1-(2-naphthylmethyl)-2,5,13-trioxo-14-oxa-3,6,12-triazahexadec-1-ylcarbamate | C48H53N5O7 | 详情 | 详情 | |
| (VIII) | 28727 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(1-trityl-1H-imidazol-5-yl)propionic acid | C40H33N3O4 | 详情 | 详情 | |
| (IX) | 28728 | 9H-fluoren-9-ylmethyl (1S,4R,7R,10S)-10-(aminocarbonyl)-7-benzyl-18,18-dimethyl-4-(2-naphthylmethyl)-2,5,8,16-tetraoxo-1-[(1-trityl-1H-imidazol-5-yl)methyl]-17-oxa-3,6,9,15-tetraazanonadec-1-ylcarbamate | C73H74N8O8 | 详情 | 详情 | |
| (X) | 18471 | N-(tert-butoxycarbonyl)-2-methylalanine | 30992-29-1 | C9H17NO4 | 详情 | 详情 |
| (XI) | 28729 | tert-butyl (4S,7R,10R,13S)-13-(aminocarbonyl)-10-benzyl-1,1,21,21-tetramethyl-7-(2-naphthylmethyl)-2,5,8,11,19-pentaoxo-4-[(1-trityl-1H-imidazol-5-yl)methyl]-20-oxa-3,6,9,12,18-pentaazadocos-1-ylcarbamate | C67H79N9O9 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)The solid-phase method of peptide synthesis, with an ABIMED AMS 422 synthesizer and a Rink amide resin have been used. N-Fmoc-L-Leucine (I) was attached to Rink amide resin using benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate as the coupling reagent, and the Fmoc protecting group was subsequently removed to afford resin (II). Further coupling and deprotection cycles with N-Fmoc-L-tyrosine(O-t--Bu) (III), N-Fmoc-N-Boc-L-lysine (V) and again N-Fmoc-N-Boc-L-lysine (V) provided peptide resins (IV), (VI) and (VII), respectively.
| 【1】 Davidson, A.; Fridkin, M.; Perl, O.; Rubinraut, S.; Gozes, I.; Ashur-Fabian, O.; Giladi, E.; Mapping the active site in vasoactive intestinal to a core of four amino acids: Neuroprotective drug design. Proc Natl Acad Sci USA 1999, 96, 7, 4143. |
| 【2】 Gozes, I.; Fridkin, M. (Yeda Research & Development Co. Ltd.); Conjugates of lipophilic moieties and fragments of vasoactive intestinal peptide (VIP). WO 9740070 . |
| 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) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (II) | 27091 | (2S)-2-amino-4-methylpentanamide | C6H14N2O | 详情 | 详情 | |
| (III) | 18858 | (2S)-3-[4-(tert-butoxy)phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C28H29NO5 | 详情 | 详情 | |
| (IV) | 27096 | (2S)-2-([(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]amino)-4-methylpentanamide | C19H31N3O3 | 详情 | 详情 | |
| (V) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (VI) | 27092 | tert-butyl (5S)-5-amino-6-([(1S)-2-[[(1S)-1-(aminocarbonyl)-3-methylbutyl]amino]-1-[4-(tert-butoxy)benzyl]-2-oxoethyl]amino)-6-oxohexylcarbamate | C30H51N5O6 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(V)The title compound was obtained by solid-phase peptide synthesis starting from N-Boc-S-(4-methylbenzyl)cysteine linked to PAM resin (I). The protected peptide template (XVII) was synthesized by sequential coupling-deprotection cycles using the appropriate combination of either Boc- or Fmoc- N-alpha-protected amino acids. The following side-chain-protected amino acid residues were assembled: Gly (III), Lys(Boc) (V), Glu(cyclohexyl ester) (VII), Lys(Boc) (V), Pro (X), Gly (III), Lys(Boc) (V), Lys(chlorobenzyloxycarbonyl) (XIV) and Lys(Boc) (XVI) to produce the peptide resins (IV), (VI), (VIII), (IX), (XI), (XII), (XIII), (XV) and (XVII), respectively. Subsequent removal of the N-terminal and the four side-chain Boc protecting groups by means of trifluoroacetic acid yielded the peptide resin (XVIII).
| 【1】 Callebaut, C.; et al.; Inhibition of HIV infection by pseudopeptides blocking viral envelope glycoprotein-mediated membrane fusion and cell death. Virology 1996, 218, 1, 181. |
| 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) | 42129 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-[(4-methylbenzyl)sulfanyl]propionic acid | C16H23NO4S | 详情 | 详情 | |
| (II) | 42130 | (2R)-2-amino-3-[(4-methylbenzyl)sulfanyl]propionic acid | 42294-52-0 | C11H15NO2S | 详情 | 详情 |
| (III) | 42131 | 2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid | 29022-11-5 | C17H15NO4 | 详情 | 详情 |
| (IV) | 42132 | (2R)-2-[(2-aminoacetyl)amino]-3-[(4-methylbenzyl)sulfanyl]propionic acid | C13H18N2O3S | 详情 | 详情 | |
| (V) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (VI) | 42133 | (10S,16R)-10-amino-2,2-dimethyl-16-[[(4-methylbenzyl)sulfanyl]methyl]-4,11,14-trioxo-3-oxa-5,12,15-triazaheptadecan-17-oic acid | C24H38N4O6S | 详情 | 详情 | |
| (VII) | 42134 | (2S)-5-(cyclohexyloxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid | 150047-85-1 | C26H29NO6 | 详情 | 详情 |
| (VIII) | 42135 | (10R,16R)-10-[(3S)-3-amino-6-(cyclohexyloxy)-2,6-dioxohexyl]-2,2-dimethyl-16-[[(4-methylbenzyl)sulfanyl]methyl]-4,11,14-trioxo-3-oxa-5,12,15-triazaheptadecan-17-oic acid | C36H56N4O9S | 详情 | 详情 | |
| (IX) | 42136 | (10S,13S,16R,22R)-10-amino-16-[4-[(tert-butoxycarbonyl)amino]butyl]-13-[3-(cyclohexyloxy)-3-oxopropyl]-2,2-dimethyl-22-[[(4-methylbenzyl)sulfanyl]methyl]-4,11,14,17,20-pentaoxo-3-oxa-5,12,18,21-tetraazatricosan-23-oic acid | C47H76N6O12S | 详情 | 详情 | |
| (X) | 34762 | (2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-pyrrolidinecarboxylic acid | 71989-31-6 | C20H19NO4 | 详情 | 详情 |
| (XI) | 42137 | (10S,13S,16R,22R)-16-[4-[(tert-butoxycarbonyl)amino]butyl]-13-[3-(cyclohexyloxy)-3-oxopropyl]-2,2-dimethyl-22-[[(4-methylbenzyl)sulfanyl]methyl]-4,11,14,17,20-pentaoxo-10-[[(2S)pyrrolidinylcarbonyl]amino]-3-oxa-5,12,18,21-tetraazatricosan-23-oic acid | C52H83N7O13S | 详情 | 详情 | |
| (XII) | 42138 | (10S,13S,16R,22R)-10-([[(2S)-1-(2-aminoacetyl)pyrrolidinyl]carbonyl]amino)-16-[4-[(tert-butoxycarbonyl)amino]butyl]-13-[3-(cyclohexyloxy)-3-oxopropyl]-2,2-dimethyl-22-[[(4-methylbenzyl)sulfanyl]methyl]-4,11,14,17,20-pentaoxo-3-oxa-5,12,18,21-tetraaz | C54H86N8O14S | 详情 | 详情 | |
| (XIII) | 42139 | (10S,13S,16R,22R)-10-[([(2S)-1-[2-([(2S)-2-amino-6-[(tert-butoxycarbonyl)amino]hexanoyl]amino)acetyl]pyrrolidinyl]carbonyl)amino]-16-[4-[(tert-butoxycarbonyl)amino]butyl]-13-[3-(cyclohexyloxy)-3-oxopropyl]-2,2-dimethyl-22-[[(4-methylbenzyl)sulfanyl] | C65H106N10O17S | 详情 | 详情 | |
| (XIV) | 42140 | (2S)-6-([[(4-chlorobenzyl)oxy]carbonyl]amino)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C29H29ClN2O6 | 详情 | 详情 | |
| (XV) | 42141 | (10S,13S,16R,22R)-10-[([(2S)-1-[(5S,8S)-8-amino-5-[4-[(tert-butoxycarbonyl)amino]butyl]-16-(4-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-anoyl]pyrrolidinyl]carbonyl)amino]-16-[4-[(tert-butoxycarbonyl)amino]butyl]-13-[3-(cyclohexyloxy) | C79H123ClN12O20S | 详情 | 详情 | |
| (XVI) | 37991 | (2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoic acid | 2483-46-7 | C16H30N2O6 | 详情 | 详情 |
| (XVII) | 42142 | (10S,13S,16R,22R)-10-[[((2S)-1-[(5S,8S,11S)-11-[(tert-butoxycarbonyl)amino]-5-[4-[(tert-butoxycarbonyl)amino]butyl]-8-[4-([[(4-chlorobenzyl)oxy]carbonyl]amino)butyl]-19,19-dimethyl-4,7,10,17-tetraoxo-18-oxa-3,6,9,16-tetraazaicos-1-anoyl]pyrrolidinyl | C95H151ClN14O25S | 详情 | 详情 | |
| (XVIII) | 42143 | (3S,6S,9R,15R)-3,9-bis(4-aminobutyl)-1-[(2S)-1-((5S,8S)-5-(4-aminobutyl)-16-(4-chlorophenyl)-8-[[(2S)-2,6-diaminohexanoyl]amino]-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-anoyl)pyrrolidinyl]-6-[3-(cyclohexyloxy)-3-oxopropyl]-15-[[(4-methylbenzyl)s | C70H111ClN14O15S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)Coupling of N-alpha-Fmoc-N-epsilon-Boc-lysine (I) to 7-amino-4-methylcoumarin (II) by means of DCC produces the lysine amide (III). After acidic cleavage of the N-Boc protecting group of (III), the resultant primary amine (IV) is attached to chlorotrityl resin to produce (V). The Fmoc group of (V) is then removed with piperidine in DMF, yielding the lysinamide-bound resin (VI). Further coupling with N-Fmoc-cyclohexylalanine (VII) employing TBTU/HOAt furnishes the dipeptide amide resin (VIII). The title compound is finally cleaved from the solid support by means of trifluoroacetic acid in CH2Cl2.
| 【1】 Saar, K.; Mazarati, A.M.; Mahlapuu, R.; Hallnemo, G.; Soomets, U.; Kilk, K.; Hellberg, S.; Pooga, M.; Tolf, B.R.; Shi, T.S.; Hökfelt, T.; Wasterlain, C.; Bartfai, T.; Langel, U.; Anticonvulsant activity of a nonpeptide galanin receptor agonist. Proc Natl Acad Sci USA 2002, 99, 10, 7136. |
| 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) | 18854 | (2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (II) | 64549 | 7-amino-4-methyl-2H-chromen-2-one | C10H9NO2 | 详情 | 详情 | |
| (III) | 64550 | 9H-fluoren-9-ylmethyl 5-[(tert-butoxycarbonyl)amino]-1-{[(4-methyl-2-oxo-2H-chromen-7-yl)amino]carbonyl}pentylcarbamate | C36H39N3O7 | 详情 | 详情 | |
| (IV) | 64551 | 9H-fluoren-9-ylmethyl 5-amino-1-{[(4-methyl-2-oxo-2H-chromen-7-yl)amino]carbonyl}pentylcarbamate | C31H31N3O5 | 详情 | 详情 | |
| (VI) | 64552 | 2,6-diamino-N-(4-methyl-2-oxo-2H-chromen-7-yl)hexanamide | C16H21N3O3 | 详情 | 详情 | |
| (VII) | 30827 | (2S)-3-cyclohexyl-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C24H27NO4 | 详情 | 详情 | |
| (VIII) | 64553 | Galnon; Fmoc-beta-cyclohexyl-Ala-Lys-AMC | 475115-35-6 | C40H46N4O6 | 详情 | 详情 |