Solid‐Phase Synthesis and Structural Study of Substituted 1,4,5,6‐Tetrahydro‐6‐oxopyridine‐3‐carboxylic Acids

Abstract

An efficient solid-phase approach to prepare substituted 1,4,5,6-tetrahydro-6-oxopyridines bearing a carboxylic acid group on C3 has been developed. The four-step protocol involves an initial acetoacetylation of polystyrene Wang resin, followed by preparation of resin-bound enamine. The cyclization reactions were carried out by reacting immobilized enamines with Knovenagel derivatives by a Hantzsch-type heterocyclization. Acidolytic cleavage from the solid support rendered the desired heterocyclic compounds in excellent yields and high purity. The synthesized compounds were structurally characterized by spectroscopic methods. In order to gain a better understanding of the structure of the obtained heterocycles, theoretical calculations at the ab initio (B3LYP/6-31G*) level were performed.

Solvent-free synthesis of novel vanillidene derivatives of Meldrum's acid: biological evaluation, DNA and BSA binding study

“…These compounds exhibit different biopotentials, such as antimalarial and antioxidant activities. 9 Also, arylidene analogues of Meldrum's acid have been reported as the key precursors in cycloaddition reactions, 10 for synthesis of mono alkyl Meldrum's acid derivatives, 11 epoxides, 12 deuterium labelled carboxylic acids, 13 oxopyridines, 14 pyridines, 15 lactones, 16 b-aryl aldehydes, 17 and for the synthesis of heterocyclic compounds of biological importance such as cardiotonic 18 and HIV integrase inhibitory activities. 19 Bering in mind the mentioned facts, there is a reasonable tendency to synthesize a novel Meldrum's acid derivatives.…”

Eco-Friendly Methodology to Prepare N-Heterocycles Related to Dihydropyridines: Microwave-Assisted Synthesis of Alkyl 4-Arylsubstituted-6-chloro-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylate and 4-Arylsubstituted-4,7-dihydrofuro[3,4-b]pyridine-2,5(1H,3H)-dione

“…In recent years, increasing interest has been focused on the synthesis of 1,4-dihydropyridine derivatives (1,4-DHPs) owing to their significant biological activity [ 10 , 11 , 12 ]. In particular, dihydropyridine drugs, such as nifedipine, nicardipine, amlodipine, and others, are effective cardiovascular agents for the treatment of hypertension [ 13 ].…”

3,4-Dihydro-2(1H)-Pyridones as Building Blocks of Synthetic Relevance

“…In 2006, our group published the first SPOS of 3,4-DHPo derivatives following a solid-support assisted synthetic strategy (Scheme 15). [60] The immobilized acetoacetate (22) was obtained by reaction of 2,2,6-trimethyl-1,3-dioxin-4-one (1), and Wang resin (0.92 mmol OH/g), the further reaction of 22 in the presence of NH4OAc and HOAc led to the corresponding immobilized enamine (23), which reacted with the Knovenagel derivatives (24) to afford the expected immobilized 3,4-DHPo (25). The heterocycle was cleaved from the resin with 71-85% overall yield (Scheme 15).…”

“…The heterocycle was cleaved from the resin with 71-85% overall yield (Scheme 15). [60] Scheme 15. SPOS of 3,4-Dihydro-2(1H)-pyridones derivatives (3,.…”