Synthesis of novel kavain-like derivatives and evaluation of their cytotoxic activity

Abstract

Reações de acoplamento do tipo Heck, Sonogashira-Hagihara, Suzuki-Miyaura e reação de aldolisação catalizadas por metal foram utilizadas para a obtenção de três séries de d-valerolactonas substituídas em posições 3, 4, 5 e 6 do anel lactônico. As 26 d-valerolactonas sintetizadas foram testadas contra três linhagens celulares e cinco delas exibiram uma moderada atividade citotóxica.Palladium-catalyzed cross coupling reactions (Sonogashira-Hagihara, Suzuki-Miyaura, and Heck) coupling and nickel hydride-mediated tandem isomerization aldolisation have been used for the synthesis of three series of d-valerolactones substituted in positions 3, 4, 5 and 6 of the lactone ring. The 26 kavaïn-like derivatives were tested against three cell lines and five of them exhibited a weak cytotoxic activity.

Peppers: A “Hot” Natural Source for Antitumor Compounds

“…Further derivatives of 52 have been evaluated against tumorigenic cells. The most active compound of the series ( 54 ), however, presented twofold higher cytotoxicity for human normal keratinocytes than for melanoma cells, impairing further studies in vivo [ 110 ]. Moreover, compounds 49–53 were also reported to be potent cytochrome P450 inhibitors and hepatotoxic [ 171 ].…”

Fluorous Supported Synthesis of Pyrazolone Derivatives From Allylic Alcohols Using a Palladium-Catalyzed Strategy

“…18,19 A more recent approach to such β-ketoesters intermediates is the conversion of allylic alcohols to ketone in a Heck coupling process. 20,21 It is obvious that described methods produce unwanted by-products (competition between 2 β-hydride eliminations in this process). In this respect, the development of an approach that allows an easy elimination of these would be of significance.…”