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【结 构 式】 
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【分子编号】22260 【品名】(2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid 【CA登记号】 |
【 分 子 式 】C23H25NO6 【 分 子 量 】411.45464 【元素组成】C 67.14% H 6.12% N 3.4% O 23.33% |
合成路线1
该中间体在本合成路线中的序号：(XIII)To the resin (VIII) were in turn incorporated the following aminoacids: N-Fmoc-L-phenylalanine (IX), N-Fmoc-tryptophan (XI), N-Fmoc-L-aspartic acid beta-t-butyl ester (XIII) and the glycosylated asparragine derivative (XV), each followed by an Fmoc deprotection step to furnish the peptide resins (X), (XII), (XIV) and (XVI), respectively.
| 【1】 Aimoto, S.; Akaji, K.; Synthesis of MEN11420, a glycosylated bicyclic peptide, by intramolecular double cyclization using a chloroimidazolinium coupling reagent. Tetrahedron 2001, 57, 9, 1749. |
| 【2】 Arcamone, F.; Maggi, C.A.; Quartara, L.; Giannotti, D. (Menarini Industrie Farma Riunite Srl); Bicyclic tachykinins antagonists, preparation thereof and their use in pharmaceutical compsn.. JP 1999501643; WO 9628467 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 56123 | (2S)-2-({(2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoyl}amino)-4-methylpentanoic acid | C14H27N3O5 | 详情 | 详情 | |
| (IX) | 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 |
| (X) | 56124 | (2S)-2-({(2S)-2-{[(2S)-2-amino-3-phenylpropanoyl]amino}-3-[(tert-butoxycarbonyl)amino]propanoyl}amino)-4-methylpentanoic acid | C23H36N4O6 | 详情 | 详情 | |
| (XI) | 56129 | (2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(1H-indol-3-yl)propanoic acid | C26H22N2O4 | 详情 | 详情 | |
| (XII) | 56125 | (2S)-2-({(2S)-2-[((2S)-2-{[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino}-3-phenylpropanoyl)amino]-3-[(tert-butoxycarbonyl)amino]propanoyl}amino)-4-methylpentanoic acid | C34H46N6O7 | 详情 | 详情 | |
| (XIII) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (XIV) | 56126 | (2S,5S,8S,11S,14S)-14-amino-8-benzyl-5-{[(tert-butoxycarbonyl)amino]methyl}-11-(1H-indol-3-ylmethyl)-2-isobutyl-18,18-dimethyl-4,7,10,13,16-pentaoxo-17-oxa-3,6,9,12-tetraazanonadecan-1-oic acid | C42H59N7O10 | 详情 | 详情 | |
| (XV) | 56127 | 2,3,4,5,6-pentafluorophenyl (2S)-4-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-4-oxobutanoate | C39H36F5N3O13 | 详情 | 详情 | |
| (XVI) | 56128 | (2S,5S,8S,11S,14S)-14-{[(2S)-4-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-amino-4-oxobutanoyl]amino}-8-benzyl-5-{[(tert-butoxycarbonyl)amino]methyl}-11-(1H-indol-3-ylmethyl)-2-isobutyl-18,18-dimethyl-4,7,10,13,16-pentaoxo-17-oxa-3,6,9,12-tetraazanonadecan-1-oic acid | C60H84N10O20 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)In an alternative procedure, initial anchoring of N-Fmoc-L-phenylalanine (IX) to the chlorotrityl resin afforded resin (XXI), which was deprotected with piperidine in DMF to provide the phenylalanine-resin (XXII). Sequential coupling and deprotection cycles with N-Fmoc-L-tryptophan (XI), N-Fmoc-L-aspartic acid beta-t-butyl ester (XIII), and N-Fmoc-N’-(tetraacetyl-beta-D-glycosyl)asparragine (XXV) yielded the peptide resins (XXIII), (XXIV) and (XXVI), respectively.
| 【1】 Aimoto, S.; Akaji, K.; Synthesis of MEN11420, a glycosylated bicyclic peptide, by intramolecular double cyclization using a chloroimidazolinium coupling reagent. Tetrahedron 2001, 57, 9, 1749. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX),(XXI) | 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 |
| (XI) | 56129 | (2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(1H-indol-3-yl)propanoic acid | C26H22N2O4 | 详情 | 详情 | |
| (XIII) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (XXII) | 13952 | (S)-(-)-Phenylalanine; L-Phenylalanine | 63-91-2 | C9H11NO2 | 详情 | 详情 |
| (XXIII) | 56133 | (2S)-2-{[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino}-3-phenylpropanoic acid | C20H21N3O3 | 详情 | 详情 | |
| (XXIV) | 56134 | (2S)-2-{[(2S)-2-{[(2S)-2-amino-4-(tert-butoxy)-4-oxobutanoyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-phenylpropanoic acid | C28H34N4O6 | 详情 | 详情 | |
| (XXV) | 56135 | (2S)-4-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-4-oxobutanoic acid | C33H37N3O13 | 详情 | 详情 | |
| (XXVI) | 56136 | (2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-4-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-amino-4-oxobutanoyl]amino}-4-(tert-butoxy)-4-oxobutanoyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-phenylpropanoic acid | C46H59N7O16 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(X)Coupling of N-(Boc)-3-methyl-L-valine (I) with L-leucine benzyl ester (II) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-HCl (EDC) and 1-hydroxybenzotriazole (HOBt) in the presence of N-ethylmorpholine gave the N-Boc-dipeptide (III), which was deprotected with trifluoroacetic acid in CH2Cl2 to afford (IV). Subsequent coupling of (IV) with N-Fmoc-2-methyl-L-phenylalanine (V) mediated by EDC and HOBt provided the N-Fmoc-tripeptide (VI). Deprotection of the fluorenylmethoxycarbonyl group of (VI) was effected with piperidine in CH2Cl2 to yield (VII). Further coupling and deprotection cycles with N-Fmoc-O-tert-butyl-L-glutamic acid (VIII) and then with N-Fmoc-O-tert-butyl-L-aspartic acid (X) provided peptides (IX) and (XI), respectively. This latter was then coupled to mono-tert--butyl succinate (XII) to furnish (XIII).
| 【1】 Attwood, M.R.; Campbell, A.D.; Bennett, J.M.; et al.; The design and synthersis of potent inhibitors of hepatitis C virus NS3-4A proteinase. Antivir Chem Chemother 1999, 10, 5, 259. |
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 22251 | (2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutyric acid;2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoic acid;N-(tert-butoxycarbonyl)-3-methyl-L-valine | 62965-35-9 | C11H21NO4 | 详情 | 详情 |
| (II) | 22252 | Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate | C13H19NO2 | 详情 | 详情 | |
| (III) | 22253 | benzyl (2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutanoyl]amino)-4-methylpentanoate | C24H38N2O5 | 详情 | 详情 | |
| (IV) | 22254 | benzyl (2S)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-4-methylpentanoate | C19H30N2O3 | 详情 | 详情 | |
| (V) | 22255 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-methylphenyl)propionic acid | C25H23NO4 | 详情 | 详情 | |
| (VI) | 22256 | benzyl (5S,8S,11S)-8-(tert-butyl)-1-(9H-fluoren-9-yl)-11-isobutyl-5-(2-methylbenzyl)-3,6,9-trioxo-2-oxa-4,7,10-triazadodecan-12-oate | C44H51N3O6 | 详情 | 详情 | |
| (VII) | 22257 | benzyl (2S)-2-[((2S)-2-[[(2S)-2-amino-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-4-methylpentanoate | C29H41N3O4 | 详情 | 详情 | |
| (VIII) | 22258 | (2S)-5-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid | 104091-08-9 | C24H27NO6 | 详情 | 详情 |
| (IX) | 22259 | benzyl (2S,5S,8S,11S)-11-amino-5-(tert-butyl)-2-isobutyl-16,16-dimethyl-8-(2-methylbenzyl)-4,7,10,14-tetraoxo-15-oxa-3,6,9-triazaheptadecan-1-oate | C38H56N4O7 | 详情 | 详情 | |
| (X) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (XI) | 22261 | 1-benzyl 16-(tert-butyl) (2S,5S,8S,11S,14S)-14-amino-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-8-(2-methylbenzyl)-4,7,10,13-tetraoxo-3,6,9,12-tetraazahexadecane-1,16-dioate | C46H69N5O10 | 详情 | 详情 | |
| (XII) | 22262 | 4-(tert-butoxy)-4-oxobutyric acid | C8H14O4 | 详情 | 详情 | |
| (XIII) | 22263 | 1-benzyl 19-(tert-butyl) (2S,5S,8S,11S,14S)-14-[2-(tert-butoxy)-2-oxoethyl]-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-8-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazanonadecane-1,19-dioate | C54H81N5O13 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(X)Coupling of N-(Boc)-3-methyl-L-valine (I) with L-leucine benzyl ester (II) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-HCl (EDC) and 1-hydroxybenzotriazole (HOBt) in the presence of N-ethylmorpholine gave the N-Boc-dipeptide (III), which was deprotected with trifluoroacetic acid in CH2Cl2 to afford (IV). Subsequent coupling of (IV) with N-Fmoc-2-methyl-L-phenylalanine (V) mediated by EDC and HOBt provided the N-Fmoc-tripeptide (VI). Deprotection of the fluorenylmethoxycarbonyl group of (VI) was effected with piperidine in CH2Cl2 to yield (VII). Further coupling and deprotection cycles with N-Fmoc-O-tert-butyl-L-glutamic acid (VIII) and then with N-Fmoc-O-tert-butyl-L-aspartic acid (X) provided peptides (IX) and (XI), respectively. This latter was then coupled to mono-tert--butyl succinate (XII) to furnish (XIII).
| 【1】 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 |
|---|---|---|---|---|---|---|
| (I) | 22251 | (2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutyric acid;2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoic acid;N-(tert-butoxycarbonyl)-3-methyl-L-valine | 62965-35-9 | C11H21NO4 | 详情 | 详情 |
| (II) | 22252 | Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate | C13H19NO2 | 详情 | 详情 | |
| (III) | 22253 | benzyl (2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutanoyl]amino)-4-methylpentanoate | C24H38N2O5 | 详情 | 详情 | |
| (IV) | 22254 | benzyl (2S)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-4-methylpentanoate | C19H30N2O3 | 详情 | 详情 | |
| (V) | 22255 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-methylphenyl)propionic acid | C25H23NO4 | 详情 | 详情 | |
| (VI) | 22256 | benzyl (5S,8S,11S)-8-(tert-butyl)-1-(9H-fluoren-9-yl)-11-isobutyl-5-(2-methylbenzyl)-3,6,9-trioxo-2-oxa-4,7,10-triazadodecan-12-oate | C44H51N3O6 | 详情 | 详情 | |
| (VII) | 22257 | benzyl (2S)-2-[((2S)-2-[[(2S)-2-amino-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-4-methylpentanoate | C29H41N3O4 | 详情 | 详情 | |
| (VIII) | 22258 | (2S)-5-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid | 104091-08-9 | C24H27NO6 | 详情 | 详情 |
| (IX) | 22259 | benzyl (2S,5S,8S,11S)-11-amino-5-(tert-butyl)-2-isobutyl-16,16-dimethyl-8-(2-methylbenzyl)-4,7,10,14-tetraoxo-15-oxa-3,6,9-triazaheptadecan-1-oate | C38H56N4O7 | 详情 | 详情 | |
| (X) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (XI) | 22261 | 1-benzyl 16-(tert-butyl) (2S,5S,8S,11S,14S)-14-amino-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-8-(2-methylbenzyl)-4,7,10,13-tetraoxo-3,6,9,12-tetraazahexadecane-1,16-dioate | C46H69N5O10 | 详情 | 详情 | |
| (XII) | 22262 | 4-(tert-butoxy)-4-oxobutyric acid | C8H14O4 | 详情 | 详情 | |
| (XIII) | 22263 | 1-benzyl 19-(tert-butyl) (2S,5S,8S,11S,14S)-14-[2-(tert-butoxy)-2-oxoethyl]-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-8-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazanonadecane-1,19-dioate | C54H81N5O13 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(A)Protection of the hydroxyphosphinyl function of Z-Phe(PO2)H (I) by treatment with AgNO3 and 1-adamantyl bromide (AdBr) affords protected compound (II). Treatment of (II) with ethyl methylacrylate (III) by means of hexamethyldisilazane provides compound (IV), which is then subjected to saponification with NaOH in EtOH, affording carboxylic acid (V). The Z protecting group of (V) is then removed with Pd/C and ammonium formate, and subsequent reaction with FmocCl in dioxane yields protected derivative (VI). Separately, on resin protected alanine (VII) is treated with piperidine/NMP for Fmoc removal to afford (VIII), which is then coupled with phosphinic derivative (VI) by means of HBTU/DIEA in NMP and then treated with piperidine/NMP for Fmoc removal, giving derivative (IX). Coupling between (IX) and FmocAsp(OtBu)OH by means of HBTU and DIEA in NMP followed by Fmoc removal with piperidine/NMP affords phosphinic peptide (X), which is then acetylated to give derivative (XI). Finally, the desired product is obtained after first treatment of (XI) with HOAc and trifluoroethanol (TFE) in CH2Cl2 for cleavage of the protected peptide from the resin, followed by removal of the protecting groups with TFA and scavengers (thioanisole, phenol, ethanedithiol and triisopropylsilane) in CH2Cl2/H2O and final separation of the diastereoisomeric forms of the resulting phosphinic peptides by HPLC.
| 【1】 Yiotakis, A.; et al.; Protection of the hydroxyphosphinyl function of phosphinic dipeptides by adamantyl. Application to the solid-phase synthesis of phosphinic peptides. J Org Chem 1996, 61, 19, 6601. |
| 【2】 Yiotakis, A.; Menard, J.; Dive, V.; Michaud, A.; Ezan, E.; Corvol, P.; Cotton, J.; Chauvet, M.-T.; Cuniasse, P. (Commissariat a l'Energie Atomique; INSERM (Institut National de la Sante et de la Recherche Medicale)); N-Terminal site selective inhibitors of human angiotensin conversion enzyme (ACE). EP 1091966; WO 0001706 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (I) | 49739 | (1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethylphosphinic acid | C16H18NO4P | 详情 | 详情 | |
| (II) | 49740 | 1-adamantyl (1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethylphosphinate | C26H32NO4P | 详情 | 详情 | |
| (III) | 49741 | Methacrylic acid ethyl ester; Ethyl methacrylate | 97-63-2 | C6H10O2 | 详情 | 详情 |
| (IV) | 49742 | ethyl (2S)-3-[(1-adamantyloxy)((1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphoryl]-2-methylpropanoate | C32H42NO6P | 详情 | 详情 | |
| (V) | 49743 | (2S)-3-[(1-adamantyloxy)((1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphoryl]-2-methylpropionic acid | C30H38NO6P | 详情 | 详情 | |
| (VI) | 49744 | (2S)-3-[(1-adamantyloxy)((1R)-1-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-phenylethyl)phosphoryl]-2-methylpropionic acid | C37H42NO6P | 详情 | 详情 | |
| (VII) | 49745 | 9H-fluoren-9-ylmethyl (1S)-2-amino-1-methyl-2-oxoethylcarbamate | C18H18N2O3 | 详情 | 详情 | |
| (VIII) | 35169 | (2S)-2-aminopropanamide | C3H8N2O | 详情 | 详情 | |
| (IX) | 49746 | 1-adamantyl (2S)-3-[[(1S)-2-amino-1-methyl-2-oxoethyl]amino]-2-methyl-3-oxopropyl[(1R)-1-amino-2-phenylethyl]phosphinate | C25H38N3O4P | 详情 | 详情 | |
| (X) | 49747 | tert-butyl (3S)-4-([(1R)-1-[(1-adamantyloxy)((2S)-3-[[(1S)-2-amino-1-methyl-2-oxoethyl]amino]-2-methyl-3-oxopropyl)phosphoryl]-2-phenylethyl]amino)-3-amino-4-oxobutanoate | C33H51N4O7P | 详情 | 详情 | |
| (XI) | 49748 | tert-butyl (3S)-3-(acetamido)-4-([(1R)-1-[(1-adamantyloxy)((2S)-3-[[(1S)-2-amino-1-methyl-2-oxoethyl]amino]-2-methyl-3-oxopropyl)phosphoryl]-2-phenylethyl]amino)-4-oxobutanoate | C35H53N4O8P | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(IX)The cyclic peptide precursor (XIV) was prepared by solid-phase synthesis on a preformed HMPB-MBHA resin. Attachment of N-Fmoc-glycine (I) to the resin by means of DCC and DMAP afforded resin (II). The Fmoc protecting group was then removed with piperidine in DMF, yielding the glycine-bound resin (III). Further couplings with the following protected amino acids: N-Fmoc-3-(aminomethyl)-5-nitrobenzoic acid (IV), N-Fmoc-L-tyrosine(O-t-butyl) (VI) and N-Fmoc-glycine (I), followed by Fmoc deprotection cycles, produced in turn the peptide resins (V), (VII) and (VIII). To peptide resin (VIII) was then coupled N-Fmoc-L-aspartic acid gamma-t-butyl ester (IX), yielding resin (X). Peptide (XI) was then liberated from the resin by means of 1% trifluoroacetic acid in CH2Cl2. The Fmoc group was subsequently removed by treatment with diethylamine in acetonitrile, giving (XII).
| 【1】 Park, H.S.; et al.; Protein surface recognition by synthetic receptors: A route to novel submicromolar inhibitors for alpha-chymotrypsin. J Am Chem Soc 1999, 121, 1, 8. |
| 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),(II) | 42131 | 2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid | 29022-11-5 | C17H15NO4 | 详情 | 详情 |
| (X),(XI) | 47339 | 2-([3-[(4S,10S)-4-[4-(tert-butoxy)benzyl]-10-[2-(tert-butoxy)-2-oxoethyl]-14-(9H-fluoren-9-yl)-3,6,9,12-tetraoxo-13-oxa-2,5,8,11-tetraazatetradec-1-yl]-5-nitrobenzoyl]amino)acetic acid | C48H54N6O13 | 详情 | 详情 | |
| (III) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (IV) | 47335 | 3-([[(9H-fluoren-9-ylmethoxy)carbonyl]amino]methyl)-5-nitrobenzoic acid | C23H18N2O6 | 详情 | 详情 | |
| (V) | 47336 | 2-[[3-(aminomethyl)-5-nitrobenzoyl]amino]acetic acid | C10H11N3O5 | 详情 | 详情 | |
| (VI) | 18858 | (2S)-3-[4-(tert-butoxy)phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | C28H29NO5 | 详情 | 详情 | |
| (VII) | 47337 | 2-([3-[([(2S)-2-amino-3-[4-(tert-butoxy)phenyl]propanoyl]amino)methyl]-5-nitrobenzoyl]amino)acetic acid | C23H28N4O7 | 详情 | 详情 | |
| (VIII) | 47338 | 2-([3-[([(2S)-2-[(2-aminoacetyl)amino]-3-[4-(tert-butoxy)phenyl]propanoyl]amino)methyl]-5-nitrobenzoyl]amino)acetic acid | C25H31N5O8 | 详情 | 详情 | |
| (IX) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (XII) | 47340 | 2-[(3-[(4S,10S)-10-amino-4-[4-(tert-butoxy)benzyl]-14,14-dimethyl-3,6,9,12-tetraoxo-13-oxa-2,5,8-triazapentadec-1-yl]-5-nitrobenzoyl)amino]acetic acid | C33H44N6O11 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(D)N-Fmoc-L-leucine (X) was coupled to the resin (IX) by means of TBTU to afford, after Fmoc deprotection with piperidine/DMF, the dipeptide-resin (XI). Sequential chain elongation by coupling with the following protected amino acids: Fmoc-3-methyl-L-valine (A), Fmoc-2-methyl-L-phenylalanine (B), Fmoc-L-glutamic gamma-tert-butyl ester (C), and Fmoc-L-aspartic beta-tert-butyl ester (D), followed by the corresponding Fmoc deprotection steps, furnished the peptide resins (XII), (XIII), (XIV) and (XV), respectively.
| 【1】 Jones, P.S.; Kay, P.B.; Wilson, F.X.; Raynham, T.M.; Hurst, D.N. (Hoffmann-La Roche, Inc.); alpha-Ketoamide derivs.. US 6187905 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 22255 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(2-methylphenyl)propionic acid | C25H23NO4 | 详情 | 详情 | |
| (D) | 22260 | (2S)-4-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-oxobutyric acid | C23H25NO6 | 详情 | 详情 | |
| (A) | 43350 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3,3-dimethylbutyric acid | 132684-60-7 | C21H23NO4 | 详情 | 详情 |
| (IX) | 47880 | (2S,3S)-3-amino-2-hydroxyheptanamide | C7H16N2O2 | 详情 | 详情 | |
| (X) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (XI) | 47882 | (2S,3S)-3-[[(2S)-2-amino-4-methylpentanoyl]amino]-2-hydroxyheptanamide | C13H27N3O3 | 详情 | 详情 | |
| (XII) | 47883 | (2S,3S)-3-[((2S)-2-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-4-methylpentanoyl)amino]-2-hydroxyheptanamide | C19H38N4O4 | 详情 | 详情 | |
| (XIII) | 47884 | (2S,3S)-3-([(2S)-2-[((2S)-2-[[(2S)-2-amino-3-(2-methylphenyl)propanoyl]amino]-3,3-dimethylbutanoyl)amino]-4-methylpentanoyl]amino)-2-hydroxyheptanamide | C29H49N5O5 | 详情 | 详情 | |
| (XIV) | 47885 | tert-butyl (4S,7S,10S,13S,16S)-4-amino-16-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-10-(tert-butyl)-13-isobutyl-7-(2-methylbenzyl)-5,8,11,14-tetraoxo-6,9,12,15-tetraazaicosan-1-oate | C38H64N6O8 | 详情 | 详情 | |
| (XV) | 47886 | tert-butyl (3S,6S,9S,12S,15S,18S)-3-amino-18-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-6-[3-(tert-butoxy)-3-oxopropyl]-12-(tert-butyl)-15-isobutyl-9-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-5,8,11,14,17-pentaazadocosan-1-oate | C46H77N7O11 | 详情 | 详情 | |
| (C) | 22258 | (2S)-5-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid | 104091-08-9 | C24H27NO6 | 详情 | 详情 |