Design, Synthesis and Cu2+ Recognition ofβ-Diketoacid and Quinoxalone Derivatives Bearing Caffeoyl or Galloyl Moieties Linked by Arylamide as Potential HIV Integrase Inhibitors

Abstract

An efficient procedure for the synthesis of caffeoyl-and galloyl-containing β-diketoacid derivatives linked by arylamide was reported by, in the key step, dissolving the corresponding phenyl methyl ketone in THF/DME in the presence of NaOMe as base and dimethyl oxalate as oxalylation reagent, and then separating the sodium ketoenolate ester. The resulting β-diketoacids underwent further condensation reaction with o-phenylenediamine to generate quinoxalone derivatives in good yield, rather than 2-benzimidazol. The preliminary ion binding properties of quinoxalone derivatives were also investigated. UV-Vis spectra showed that these compounds could selectively recognize Cu 2＋ ion in ethanol and form a 1∶2 complex.

Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substitutedl-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

“…45,46 For DCTAs, the linker between the core tartaric acid and the catechol can be varied with little affect on antiviral potency. For example, it can be from 0 to 4 carbon atoms and can be either sp 3 or sp 2 hybridized without losing antiviral potency.…”

“…The resulting suspension was sonicated for 5 min and filtered to give 2-(4-caffeoylaminophenyl)-2-hydroxy-4-oxo-2-butenoic acid (4) as a yellow solid (68%): mp 110°C (dec); 1 H NMR (THF-d 8 Compound 22m was converted by procedure C to 4-(3-caffeoylaminophenyl)-2-hydroxy-4-oxo-2-butenoic acid (5) as a yellow solid (62%) after the crude product was purified by HPLC: mp 137°C (dec); lit. 46 Methyl 1-(4-Fluorobenzyl)-1H-pyrrole-2-carboxylate (25). To a suspension of 60% sodium hydride (2.4 g, 0.06 mol) in DMF (100 mL) was slowly added methyl 2-pyrrolecarboxylate (6.4 g, 0.05 mol).…”

“…45 Acetophenone 21p was converted by procedure A to methyl 4-(4-(3,4-dimethoxycinnamoylamino)phenyl)-2-hydroxy-4-oxo-2-butenoate (22p) as a yellow solid (96%) after washing the crude product with 3-5 mL of ethyl acetate: mp 206°C (dec); lit. 46 A solution of 22o in CH 2 Cl 2 was cooled to -78°C and then treated dropwise with 12 equiv of 1.0 M BBr 3 in CH 2 Cl 2 . After the resulting mixture was stirred at -78°C for 3 h, the acetonedry ice bath was removed and the stirring continued at room temperature for another 6.5 h. The resulting suspension was cooled to -78°C and the reaction quenched with ice-water.…”

Design and Synthesis of p/m‐[p‐(un)Substituted Phenylsulfonamido]phenyl β‐Diketo Acids and Quinoxalone Derivatives

“…23 Therefore, as shown in Scheme 1, treatment of the [p-(un)substituted phenyl]sulfonyl chloride 1 with p/m-aminoacetophenone 2 or 3 in the presence of triethylamine in dichloromethane afforded the sulfonamide-substituted acetophenone 4 or 5. The latter underwent Claisen condensation with dimethyl oxalate in the presence of the freshly prepared NaOMe as a condensing reagent in THF/DME mixed solvent (volume ratio＝1∶1), and subsequent hydrolysis of the methyl ester 6 or 7 with 1 mol•L -1 aqueous sodium hydroxide in methanol/THF resulted in the formation of p/m-[p-(un)substituted phenylsulfonamido]phenyl 1,3-diketoacid derivatives 8 or 9.…”

Electrochemical oxidation of catechols in the presence of 4-amino-3-methyl-5-mercapto-1,2,4-triazole bearing two nucleophilic groups

“…As part of our continuing efforts directed towards the development of potential HIV-1 integrase inhibitors derived from polyhydroxylated aromatics, we have investigated the chemical and electrochemical synthesis of polyhydroxylated aromatics [20][21][22][23], such as caffeic acid and gallic acid derivatives. In the present work, we reported on the electrochemical oxidation of catechols in the presence of 4-amino-3-methyl-5-mercapto-1,2,4-triazole, bearing two nucleophilic functional groups (-SH and -NH 2 ) and investigated the effect of various electrolytic conditions on the yields of products, such as different electrode materials, amount of electricity passed, pH of the electrolytic solution and cell configuration (divided or undivided cell).…”