Synthesis of novel spiropiperidine derivatives and their antimicrobial and antioxidant activities

摘要

A series of novel spiro-piperidinyl pyrazolones are synthesized by the reaction of N-Boc protected ethyl nipecotate with heteroaryl and alkyl aldehydes in presence of lithium diisopropyl amide (LDA) to yield corresponding beta-hydroxy ester, followed by MnO2 oxidation to give beta-keto ester. Further reaction of beta-keto ester with hydrazine hydrate results in the formation of spiro-piperidinyl pyrazolone scaffold 5a-d which upon N-benzylation followed by deprotection yields compounds 7a-s. The pyrazolone-NH group has been alkylated in compound 5a with ethyl chloroacetate followed by hydrolysis and amide coupling to afford compounds 9a-d. The furan ring in compound 5a is oxidized to carboxylic acid with KMnO4 and coupled with amines to prepare amide derivatives 11a-c. All the synthesized compounds are evaluated for their in vitro antibacterial and antioxidant activity. Compounds 7a-d and 7g-s are found to possess high antibacterial activity and compounds 7a,7b, 9a, 9b, 11a and 11c are found to be potent antioxidants.