Synthesis of α- and β-lapachone derivatives from hetero diels-alder trapping of alkyl and aryl o-quinone methides

Abstract

Foram sintetizados, em um único pote reacional, alguns derivados da αe β-lapachonas a partir de reação de hetero Diels-Alder, em etanol aquoso, entre estirenos substituídos (como dienófilos) e o-quinonas metídeos (o-QMs) metilênicas e arílicas geradas por condensação de Knoevenagel da 2-hidróxi-1,4-naftoquinona com formaldeído e aldeídos aromáticos. Methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes, undergo facile hetero Diels-Alder reaction with some substituted styrenes (as dienophiles) in aqueous ethanol media providing derivatives of αand β-lapachone.

Gas‐phase reactivity of 2‐hydroxy‐1,4‐naphthoquinones: a computational and mass spectrometry study of lapachol congeners

“…Many researchers have devoted their studies to the preparation and rapid characterization of quinonoids . In this sense, electrospray ionization tandem mass spectrometry (ESI‐MS/MS) has been increasingly utilized for the structural elucidation and characterization of new natural compounds, and this technique has recently been applied to the analysis of routes for the synthesis of natural products .…”

“…In this context, our research group has concentrated efforts on the investigation of lapachol (Q4) by means of high‐resolution ESI‐MS/MS experiments in combination with computational chemistry . We have evaluated the protonated, deprotonated and cationized molecules, and we have elucidated the fragmentation mechanism on the basis of electronic structure calculations.…”

Synthesis and anti-Trypanosoma cruzi activity of β-lapachone analogues

“…In a previous communication, we reported the synthesis of six b-lapachone analogues by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with paraformaldehyde or arylaldehydes followed by a hetero-DielseAlder reaction with substituted styrenes in aqueous ethanol media, generating six b-lapachone analogues [18]. In the present work, 16 derivatives were synthesized and assayed against the infective bloodstream form of T. cruzi.…”

Synthetic 1,4-Pyran Naphthoquinones Are Potent Inhibitors of Dengue Virus Replication

“…The methodology for synthesis of the pyran naphthquinones used in this study has been reported elsewhere [ 39 , 40 ]. Briefly, the compounds were obtained by reacting of lawsone (7, 2-hydroxy-1,4-naphthoquinone) with an appropriate aldehyde (formaldehyde or arylaldehydes) that generate in situ an o-quinone methide intermediate (o-QM, via the Knoevenagel condensation, which then undergoes a hetero Diels-Alder reaction with an appropriate dienophiles.…”

“…The scope of this three-components reaction is not limited of any aldehyde . At the end of the reaction the products were purified by column chromatography using silica gel and its characterization by spectroscopic techniques was previously published [ 39 , 40 ].…”