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【结 构 式】 
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【分子编号】49150 【品名】Diethylenetriaminepentaacetic acid; N,N-Bis[2-(2,6-dioxomorpholino)ethyl]glycine 【CA登记号】23911-26-4 |
【 分 子 式 】C14H19N3O8 【 分 子 量 】357.32028 【元素组成】C 47.06% H 5.36% N 11.76% O 35.82% |
合成路线1
该中间体在本合成路线中的序号：(III)The selective protection of D-Phe1-octreotide peptide (I) with Boc2O gives the monoprotected peptide (II), which is condensed with diethylenetriaminopentaacetic acid (DTPA) dianhydride (III) by means of NaHCO3 in dioxane/water to yield the adduct (IV). The treatment of (IV) with TFA affords the desired DTPA-octreotide derivative (V), which is finally labeled with 111InCl3 in acetic acid or in ammonium citrate to afford the target indium derivative. The starting D-Phe1-octreotide peptide (I) has been obtained by the conventional methods of peptide synthesis using a peptide synthesizer.
| 【1】 Wu, Y.-T.; et al.; Direct solid phase synthesis of biologically active peptide alcohols. J Chin Chem Soc (Taipei) 1999, 46, 2, 135. |
| 【2】 Edwards, W.B.; et al.; Generally applicable, convenient solid-phase synthesis and receptor affinities of octreotide analogs. J Med Chem 1994, 37, 22, 3749. |
| 【3】 Hsieh, H.-P.; et al.; Direct solid-phase synthesis of octreotide conjugates: Precursors for use as tumor-targeted radiopharmaceuticals. Bioorg Med Chem 1999, 7, 9, 1797. |
| 【4】 Arano, Y.; et al.; Conventional and high-yield synthesis of DTPA-conjugated peptides: Application of a monoreactive DTPA to DTPA-D-Phe1-octreotide synthesis. Bioconjugate Chem 1997, 8, 3, 442. |
| 【5】 Bakker, W.H.; et al.; [111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: Synthesis, radiolabeling and in vitro validation. Life Sci 1991, 49, 22, 1583. |
| 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) | 62878 | (4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-{[(2R)-2-amino-3-phenylpropanoyl]amino}-16-benzyl-7-[(1R)-1-hydroxyethyl]-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacyclo | C49H66N10O10S2 | 详情 | 详情 | |
| (II) | 62879 | tert-butyl 4-[(4R,7S,10S,13R,16S,19R)-19-{[(2R)-2-amino-3-phenylpropanoyl]amino}-16-benzyl-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17- | C54H74N10O12S2 | 详情 | 详情 | |
| (III) | 49150 | Diethylenetriaminepentaacetic acid; N,N-Bis[2-(2,6-dioxomorpholino)ethyl]glycine | 23911-26-4 | C14H19N3O8 | 详情 | 详情 |
| (IV) | 62880 | 2-[{2-[((1R)-1-benzyl-2-{[(4R,7S,10S,13R,16S,19R)-16-benzyl-10-{4-[(tert-butoxycarbonyl)amino]butyl}-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8 | C68H93N13O20S2 | 详情 | 详情 | |
| (V) | 62881 | (13R)-14-{[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-16-benzyl-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-19-yl]am | C63H87N13O19S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of diethylenetriamine-pentaacetic acid (I) with acetic anhydride in hot pyridine gives the dianhydride (II), which is treated with 2-methoxyethylamine (III) in hot acetonitrile or isopropanol to yield the diamide ligand (IV). Finally, this compound is treated with Gd2O3 in hot water/isopropanol/acetonitrile or other mixed solvents to afford the target gadolinium complex.
| 【1】 Geraldes, C.F.G.C.; et al.; Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents. Magn Reson Imaging 1995, 13, 3, 401. |
| 【2】 White, D.H.; Moore, D.A.; deLearie, L.; Lin, W.H. (Mallinckrodt Medical Inc.); Process for manufacturing DTPA-bis amide magnetic resonance imaging. US 5508388 . |
| 【3】 Periasamy, M.P.; Weber, R.W. (Mallinckrodt Medical Inc.); Novel magnetic resonance imaging agents. WO 9001024 . |
| 【4】 Periasamy, M.; et al.; The synthesis and screening of nonionic gadolinium (III) DTPA-bisamide complexes as magnetic resonance imaging contrast agents. Invest Radiol 1991, 26, Suppl. 1, S217. |
| 【5】 White, D.H.; et al.; Synthesis and characterization of nonionic paramagnetic metal complexes as potential magnetic resonance imaging contrast agents. Invest Radiol 1990, 25, Suppl. 1, S56. |
| 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) | 55225 | 2-(bis{2-[bis(carboxymethyl)amino]ethyl}amino)acetic acid | C14H23N3O10 | 详情 | 详情 | |
| (II) | 49150 | Diethylenetriaminepentaacetic acid; N,N-Bis[2-(2,6-dioxomorpholino)ethyl]glycine | 23911-26-4 | C14H19N3O8 | 详情 | 详情 |
| (III) | 34675 | 2-methoxyethylamine; 2-methoxy-1-ethanamine | 109-85-3 | C3H9NO | 详情 | 详情 |
| (IV) | 55226 | 8,11-bis(carboxymethyl)-14-{2-[(2-methoxyethyl)amino]-2-oxoethyl}-6-oxo-2-oxa-5,8,11,14-tetraazahexadecan-16-oic acid | C20H37N5O10 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The title bis-amide was prepared by condensation of the dianhydride (I) with 5-amino-1,3,4-thiadiazole-2-sulfonamide (II).
| 【1】 Supuran, C.T.; Muncione, F.; Scozzafava, A.; Mincione, G.; Menabuoni, L.; Carbonic anhydrase inhibitors: Synthesis of sulfonamides incorporating DTPA tails and of their zinc complexes with powerful topical antiglaucoma properties. Bioorg Med Chem Lett 2001, 11, 4, 575. |
合成路线4
该中间体在本合成路线中的序号：(IV)Adenosylcobalamin-b-monocarboxylic acid (I) was coupled to 1,4-butanediamine (II) in the presence of EDC and HOBt to afford the N-(4-aminobutyl)amide (III). Subsequent acylation of amino amide (III) by diethylenetriaminopentaacetic dianhydride (IV) gave rise to the title compound.
| 【1】 Hogenkamp, H.P.C.; Collins, D.A.; Transcobalamin II receptor imaging via radiolabeled diethylene-triaminepentaacetate cobalamin analogs. J Nucl Med 1997, 38, 5, 717. |
| 【2】 Collins, D.A.; Hogenkamp, H.P.C. (Mayo Foundation for Medical Education and Research; University of Minnesota); Radionuclide labeling of vitamin B12 and coenzymes thereof. WO 9718231 . |
合成路线5
该中间体在本合成路线中的序号：(II)The resin-bound A-beta(3-40) amyloid peptide (I) is prepared by solid-phase synthesis, employing Fmoc chemistry. Acylation of the peptide-resin (I) with diethylenetriaminepentaacetic (DTPA) dianhydride (II) gives rise to the peptide DTPA-amide (III), which is further liberated from the resin to produce (IV)
| 【1】 Marshall, J.R.; et al.; Noninvasive imaging of peripherally injected Alzheimer's disease type synthetic A beta amyloid in vivo. Bioconjugate Chem 2002, 13, 2, 276. |