Synthesis and Antioxidant Activity Evaluation of Some Novel Aminocarbonitrile Derivatives Incorporating Carbohydrate Moieties

Abstract

In this study, a multicomponent reaction involving carbohydrates, β-dicarbonyl compounds, and malononitrile was disclosed to synthesize a new class of polyhydroxy compounds incorporating pyrano[2,3- d ]pyrimidine, pyrido[2,3- d ]pyrimidine and chromene heterocycles under mild conditions. For the synthesis of this class of compounds, glucose, galactose, arabinose, maltose, and lactose were used as aldehyde component in the reaction with barbituric acid and malononitrile to produce pyrano[2,3- d ]pyrimidine derivatives. By use of 1,3-cyclohexanedione instead of barbituric acid, chromene derivatives incorporating carbohydrate moieties were obtained. Also, the four-component condensation reaction between d -glucosamine, aldehyde, malononitrile, and barbituric acid was efficiently provided polyhydroxy-substituted pyrido[2,3- d ]pyrimidine derivatives. This new combinatorial approach gave a range of carbohydrate-derived heterocycles in good to excellent yields with high potential biological applications. The antioxidant activities were evaluated using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant measuring system, and the data were expressed as Trolox equivalent antioxidant capacity. All of these compounds display significant antioxidant activity. The maximum and minimum antioxidant activities were observed for 4j and 6b , respectively. Our results indicated encouraging perspectives for the improvement and usage of this type of synthetic compounds, indicating significant levels of antioxidant activity.

Synthesis of Biologically Active Molecules through Multicomponent Reactions

“…A combinatorial approach carried out by Dangolani, et al, allowed obtaining a wide range of heterocyclic compounds [76]. In order to obtain the pyrano[2,3-d]pyrimidines 77, diverse carbohydrates 76 such as glucose, galactose, arabinose, maltose and lactose reacted with barbituric acid (27a) and malononitrile/diethylmalonate (12)/(38) in ethanol and PTSA as catalyst, in a three-component fashion.…”

Cycloamination strategies for renewable N-heterocycles

“…[281][282][283] All together with glucosamine, aldehyde, and barbituric acid, addition of malononitrile is able to allow a four-component condensation reaction, giving polyhydroxy-substituted pyrido [2,3-d]pyrimidines in good yields (89-94%) catalyzed by para-toluenesulfonic acid in ethanol heated at 50°C. 284 Multicomponent condensation reactions can be used for the synthesis of pyridine-fused heterocycles. For example, Shpuntov et al showed that a three-component Mannich-type reaction of 2-alkylfuran, methyl 2-formylbenzoate, and carbamate in the presence of iodine at 0°C for 2 h affords N-Boc-1-[2-(carbomethoxy)aryl]furfurylamines in moderate yields (51-89%), and further application of a two-step reaction process of oxidative furan-ring cleavage and N-Boc deprotection catalyzed by meta-chloroperoxybenzoic acid and HCl, respectively, gives 6H-isochromeno-[4,3-b]pyridin-6-ones in moderate yields (61-68%).…”

Multicomponent Reactions for Integrating Multiple Functional Groups into an Antioxidant

“…is equivalent to 3.208 μM Trolox (21). [13] The equation 4in Figure 2 exemplifies another Knoevenagel-related MCR, in which 4hydroxy-6-methyl-2H-pyran-2-one (22) as the reagent takes part in two reactions. Firstly, 22 carries out the Knoevenagel reaction with 2,3,4-trihydroxybenzaldehyde (23) to give an intermediate (24).…”

“…We attempt to integrate more nitrogen atoms into Nheterocycle by using Groebke 3CR twice. As shown as equation (13) in Figure 5, the Groebke 3CR of o-phenylenediamine (74) and 2-(4-formylphenyl)chromen-4-one (79) with 2,4,4-trimethylpentan-2-yl isocyanide (75) allows achieving 1,4-dihydroquinoxaline (82), followed by the aromatization with 2,3-dicyano-5,6-dichlorobenzoquinone (77) and the hydrolysis with HCl to afford 2-aminoquinoxaline (83). Then, 83 acts as the reagent to participate in another Groebke 3CR with aldehyde (28) and tert-butyl isocyanide (80) under catalyzed by (CH 3 ) 3 SiCl for achieving an imidazo[1,2-a] quinoxaline (84).…”

“…The ability of 1.0 μM 19 to quench 2,2’‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonate) cationic radical ( 20 , ABTS + . ) is equivalent to 3.208 μM Trolox ( 21 ) [13] . The equation (4) in Figure 2 exemplifies another Knoevenagel‐related MCR, in which 4‐hydroxy‐6‐methyl‐2 H ‐pyran‐2‐one ( 22 ) as the reagent takes part in two reactions.…”