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【结 构 式】 
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【分子编号】46006 【品名】(2R)-3-[4-[(2,6-dichlorobenzyl)oxy]phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid 【CA登记号】112402-12-7 |
【 分 子 式 】C31H25Cl2NO5 【 分 子 量 】562.44864 【元素组成】C 66.2% H 4.48% Cl 12.61% N 2.49% O 14.22% |
合成路线1
该中间体在本合成路线中的序号：(XVI)3-Iodobenzoic acid (I) was converted to ethyl ester (II) by treatment with DCC and DMAP in ethanol. Subsequent Suzuki coupling of (II) with 2-formylbenzeneboronic acid (III) furnished the biphenyl derivative (IV). Formation of oxime (V) using hydroxylamine hydrochloride, followed by reduction with zinc metal and HOAc, afforded To derivative (XIII) were sequentially incorporated the following protected amino acids: Fmoc-D-tryptophan (XIV) and Fmoc-L-tyrosine(2,6-Cl2Bzl) (XVI), each followed by a deprotection step with piperidine in DMF, to yield the resin-bound peptides (XV) and (XVII), respectively. Cleavage of the linear intermediate (XVIII) from the resin was accomplished by treatment with trifluoroacetic acid. This intermediate was cyclized by means of HATU to give (XIX). Finally, the side-chain protecting groups of (XIX) were removed by transfer hydrogenation to afford the title compound. (Scheme 29421701b)
| 【1】 DeGrado, W.F.; Singh, G.; Reisine, T.; Suich, D.J.; Liapakis, G.; Mousa, S.A.; Template-constrained cyclic peptide analogues of somatostatin: Subtype-selective binding to somatostatin receptors and antiangiogenic activity. Bioorg Med Chem 2000, 8, 9, 2229. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII),(XVIII) | 46003 | 2'-((4S,7S)-7-[[(2R)-2-[((2R)-2-amino-3-[4-[(2,6-dichlorobenzyl)oxy]phenyl]propanoyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-isopropyl-3,6,13-trioxo-15-phenyl-14-oxa-2,5,12-triazapentadec-1-yl)[1,1'-biphenyl]-3-carboxylic acid | C60H63Cl2N7O9 | 详情 | 详情 | |
| (XIII) | 46000 | 2'-[(4S,7S)-7-amino-4-isopropyl-3,6,13-trioxo-15-phenyl-14-oxa-2,5,12-triazapentadec-1-yl][1,1'-biphenyl]-3-carboxylic acid | C33H40N4O6 | 详情 | 详情 | |
| (XIV) | 46005 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-[5-[(Z)-1-propenyl]-4-vinyl-1H-pyrrol-3-yl]propionic acid | C27H26N2O4 | 详情 | 详情 | |
| (XV) | 46002 | 2'-((4S,7S)-7-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-4-isopropyl-3,6,13-trioxo-15-phenyl-14-oxa-2,5,12-triazapentadec-1-yl)[1,1'-biphenyl]-3-carboxylic acid | C44H50N6O7 | 详情 | 详情 | |
| (XVI) | 46006 | (2R)-3-[4-[(2,6-dichlorobenzyl)oxy]phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid | 112402-12-7 | C31H25Cl2NO5 | 详情 | 详情 |
| (XIX) | 46004 | benzyl 4-[(11S,14S,17R,20S)-20-[4-[(2,6-dichlorobenzyl)oxy]benzyl]-17-(1H-indol-3-ylmethyl)-11-isopropyl-10,13,16,19,22-pentaoxo-9,12,15,18,21-pentaazatricyclo[21.3.1.0(2,7)]heptacosa-1(27),2,4,6,23,25-hexaen-14-yl]butylcarbamate | C60H61Cl2N7O8 | 详情 | 详情 |