A Practical Route for the Preparation of 1,4,7-Triazacyclononanyl Diacetates with a Hydroxypyridinonate Pendant Arm

Abstract

Abstract:The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The method is suitable for rapid syntheses of metal chelator HOPO-TACNs of biomedical interest.

New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64: Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging

“…The alcohol group in 3 was brominated with N -bromosuccinimide and triphenylphosphine to its corresponding bromide 4 as a yellow oil. The introduction of the third carboxylate arm with an additional nitro-functional unit to the chelator NOTA backbone was carried out by the coupling reaction between 4 and di- tert -butyl 2,2′-(1,4,7-triazonane-1,4-diyl)diacetate (NO2A- t- Bu) 26 in the presence of anhydrous K 2 CO 3 in acetonitrile to yield the crucial intermediate 5 , which was purified by column chromatography to obtain a white waxy solid. Deprotection of the tert -butyl group was achieved by treating compound 5 with trifluoroacetic acid (TFA) in methylene dichloride (DCM) at room temperature to afford the TFA salt of p -NO 2 -PhPr-NE3TA ( 6 ) as an oil, and the trace amount of water in the oil was removed by coevaporating the product with 20 mL CHCl 3 three times.…”

“…To a solution of NO2A t Bu 26 (1 g, 2.8 mmol) in 10 mL of MeCN was added ethyldiisopropylamine (DIEA) (0.72 g, 5.6 mmol) and 4 (1.12 g, 2.8 mmol). The reaction mixture was left at room temperature overnight.…”

Synthesis of novel Iron(III) chelators based on triaza macrocycle backbone and 1-hydroxy-2(H)-pyridin-2-one coordinating groups and their evaluation as antimicrobial agents

“…Very few polyaza macrocycles bearing HOPO coordinating groups have been described [48,[51][52][53][54]. Macrocycles offer the potential to fine tune the metal chelating properties by varying the cycle's size and fexibility.…”

Universal Molecular Scaffold for Facile Construction of Multivalent and Multimodal Imaging Probes

“…The amino group of 2 was converted to azide through a diazotransfer reaction, 16 and then the resulting compound 3 was tosylated to afford compound 4. Compound 5 was obtained via alkylation of NO2A( t Bu) (di- tert -butyl 2,2′-(1,4,7-triazonane-1,4-diyl)diacetate) 17 using compound 4 . Hydrolysis of methyl ester of 5 resulted in the BFC 6 .…”