A Multicomponent Reaction for the One-Pot Synthesis of 4-Aza-2,3-didehydropodophyllotoxin and Derivatives

Abstract

[reaction: see text] A convergent method has been found to prepare 4-aza-2,3-didehydropodophyllotoxin and derivatives in a one-pot procedure. The mechanism of the reaction between tetronic acid, anilines, and benzaldehydes is discussed.

N-Hydroxyethyl-4-aza-didehydropodophyllotoxin derivatives as potential antitumor agents

“…The synthesis of compounds 7a–e , 8a , 8c , 8d and 9a–d described in this study are reported previously by our group using a one pot simple reflux in ethanol (Kumar and Alegria, 2010) following the synthetic procedure used for preparing 4-aza-2,3-didehydropodophyllotoxin derivatives, as reported by Tratrat et al (2002). A patent reported by Husson and his group also claims the synthesis of one of these derivatives ( 7a ), however, no characterization data of this compound has been given in that report (Husson et al, 2003).…”

“…Even if such initial compounds might have diminished cytotoxic potencies compared with the parent cyclolignan, the ease of preparation of carefully designed libraries of analogs would lead to more informative SAR studies and expeditious structure optimization. The synthetic efforts for such libraries were reduced to an one-step synthesis when Giorgi-Renault and Husson disclosed a multi component reaction (MCR) leading to the synthesis of 4-aza-2,3-dihehydropodophyllotoxins as promising anticancer drug leads (Tratrat et al, 2002). Earlier, an important contribution in this context was made by demonstrating that simplified 4-aza-2,3-didehydropodophyllotoxins 4–6 (Fig.…”

Design, Synthesis, and Biological Evaluation of the First Podophyllotoxin Analogues as Potential Vascular‐Disrupting Agents

“…[16] The notable advantages of this method are mild conditions without activation, fast reaction times, and tolerance for structural diversity. Therefore, we decided to use this reaction for the preparation of the new carbon homologated analogues using the corresponding aldehydes.…”

Highly active magnetically separable CuFe2O4 nanocatalyst: an efficient catalyst for the green synthesis of tetrahydrofuro[3,4-b]quinoline-1,8(3H,4H) dione derivatives

“…Among them, derivatives of 4-azapodophyllotoxin ( Fig. 1), were reported as powerful DNA topoisomerase II inhibitors, substitution of carbon atom at position 4 of podophyllotoxin by nitrogen atom would bring about great changes in the biological profile working through a mechanism of action entirely different from that of the parent natural podophyllotoxin [33][34][35][36].…”