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【结 构 式】 
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【分子编号】27842 【品名】(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propionic acid 【CA登记号】 |
【 分 子 式 】C24H23NO5 【 分 子 量 】405.45036 【元素组成】C 71.1% H 5.72% N 3.45% O 19.73% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The reaction of N-(tert-butoxycarbonyl)-L-phenylalanine-N-carboxyanhydride (I) with N-methylethylenediamine (II) gives the phenyalaninamide (III), which is condensed with the N-protected chiral azetidinone (IV) by means of Cs2CO3 to yield the diaminopropionic acid derivative (V). The condensation of (V) with glycine tert-butyl ester (VI) by means of BOP and DIEA affords the peptide (VII), which, after deprotection with H2 over Pd/C, is condensed with 4-O-benzyl-L-tyrosine (VIII) by means of BOP and DIEA giving the acyclic precursor (IX). The deprotection of (IX) with TFA, followed by cyclization by means of EDC, HOAt, DIEA and DCM in DMF provides the protected cyclic precursor (X), which is finally deprotected by hydrogenation with H2 over Pd black in ethanol.
| 【1】 DeHaven, R.; Dang, T.; Daubert, J.; Yaksh, T.L.; Zhang, L.; Goodman, M.; Shreder, K.; Umeno, H.; Synthesis and biological activity of a novel methylamine-bridged enkephalin analogue (MABE): A new route to cyclic peptides and peptidomimetics. J Med Chem 1998, 41, 14, 2631. |
| 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) | 27837 | tert-butyl (4S)-4-benzyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate | 142955-51-9 | C15H17NO5 | 详情 | 详情 |
| (II) | 27777 | N-(2-aminoethyl)-N-methylamine | 109-81-9 | C3H10N2 | 详情 | 详情 |
| (III) | 27838 | tert-butyl (1S)-1-benzyl-2-[[2-(methylamino)ethyl]amino]-2-oxoethylcarbamate | C17H27N3O3 | 详情 | 详情 | |
| (IV) | 27845 | benzyl (3R)-2-oxooxetanylcarbamate | C11H11NO4 | 详情 | 详情 | |
| (V) | 27839 | (6S,13R)-6-benzyl-13-[[(benzyloxy)carbonyl]amino]-2,2,11-trimethyl-4,7-dioxo-3-oxa-5,8,11-triazatetradecan-14-oic acid | C28H38N4O7 | 详情 | 详情 | |
| (VI) | 27841 | tert-butyl 2-aminoacetate;tert-butyl glycinate;Glycine tert-butyl ester | 6456-74-2 | C6H13NO2 | 详情 | 详情 |
| (VII) | 27840 | tert-butyl (6S,13R)-6-benzyl-13-[[(benzyloxy)carbonyl]amino]-2,2,11-trimethyl-4,7,14-trioxo-3-oxa-5,8,11,15-tetraazaheptadecan-17-oate | C34H49N5O8 | 详情 | 详情 | |
| (VIII) | 27842 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propionic acid | C24H23NO5 | 详情 | 详情 | |
| (IX) | 27843 | tert-butyl (6S,13R)-6-benzyl-13-([(2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propanoyl]amino)-2,2,11-trimethyl-4,7,14-trioxo-3-oxa-5,8,11,15-tetraazaheptadecan-17-oate | C50H64N6O10 | 详情 | 详情 | |
| (X) | 27844 | benzyl (1S)-2-[[(6S,12R)-6-benzyl-1-methyl-5,8,11-trioxo-1,4,7,10-tetraazacyclotridecan-12-yl]amino]-1-[4-(benzyloxy)benzyl]-2-oxoethylcarbamate | C41H46N6O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The title compound is prepared by solid-phase peptide synthesis starting from N-Fmoc-L-phenylalanine attached to Wang resin (I). Deprotection of (I) with piperidine in NMP removes the N-Fmoc group, yielding the phenylalanine resin (II). Coupling of (II) with N-trityl glycine (III) in the presence of PyBOP and HOBt, followed by acidic cleavage of the N-trityl group furnishes the dipeptide derivative (IV). To this is assembled N-Fmoc-S-trityl-D-penicillamine (V), followed by deprotection with piperidine in NMP, to produce resin (VI). Subsequent coupling of (VI) with N-Cbz-O-benzyl-L-tyrosine (VII) leads to the protected tetrapeptide (VIII). Removal of the S-trityl protecting group of (VIII) employing trifluoroacetic acid provides thiol (IX).
| 【1】 Rew, Y.; Malkmus, S.; Svensson, C.; Yaksh, T.L.; Chung, N.N.; Schiller, P.W.; Cassel, J.A.; DeHaven, R.; Goodman, M.; Synthesis and biological activities of cyclic lanthionine enkephalin analogues: delta-Opioid receptor selective ligands. J Med Chem 2002, 45, 17, 3746. |
| 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) | 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 |
| (II) | 13952 | (S)-(-)-Phenylalanine; L-Phenylalanine | 63-91-2 | C9H11NO2 | 详情 | 详情 |
| (III) | 63269 | 2-(tritylamino)acetic acid | C21H19NO2 | 详情 | 详情 | |
| (IV) | 63270 | (2S)-2-[(2-aminoacetyl)amino]-3-phenylpropanoic acid | C11H14N2O3 | 详情 | 详情 | |
| (V) | 63271 | (2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-methyl-3-(tritylsulfanyl)butanoic acid | C39H35NO4S | 详情 | 详情 | |
| (VI) | 63272 | (2S)-2-[(2-{[(2S)-2-amino-3-methyl-3-(tritylsulfanyl)butanoyl]amino}acetyl)amino]-3-phenylpropanoic acid | C35H37N3O4S | 详情 | 详情 | |
| (VII) | 27842 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[4-(benzyloxy)phenyl]propionic acid | C24H23NO5 | 详情 | 详情 | |
| (VIII) | 63273 | (5S,8S,14S)-14-benzyl-5-[4-(benzyloxy)benzyl]-8-[1-methyl-1-(tritylsulfanyl)ethyl]-3,6,9,12-tetraoxo-1-phenyl-2-oxa-4,7,10,13-tetraazapentadecan-15-oic acid | C59H58N4O8S | 详情 | 详情 | |
| (IX) | 63274 | (5S,8S,14S)-14-benzyl-5-[4-(benzyloxy)benzyl]-8-(1-methyl-1-sulfanylethyl)-3,6,9,12-tetraoxo-1-phenyl-2-oxa-4,7,10,13-tetraazapentadecan-15-oic acid | C40H44N4O8S | 详情 | 详情 |