Convergent First Total Synthesis of Melovinone: A Densely Substituted 3-Methoxy-4-quinolone Isolated from Melochia tomentosa L.

AGUILAR, ABEL A. ARROYO; LEDESMA, GABRIELA N.; TIRLONI, BáRBARA; KAUFMAN, TEODORO S.; LARGHI, ENRIQUE L.

SYNTHESIS-STUTTGART

GEORG THIEME VERLAG KG

Año: 2019

0039-7881

The first total synthesis of melovinone, anonrutaceous 3-methoxy-4-quinolone alkaloid isolated from Melochia tomentosa L., is reported. The target was acquired in aconvergent fashion, through the Suzuki-Miyaura coupling between an ortho-nitrobenzoic acid acetonyl esterderivative prepared from vanillin and 5-phenyl-1-pentyl potassiumtrifluoroborate, obtained from â-phenethyl bromide. This was followed by a chemoselectivereduction of the nitro group, and a microwave-assisted AcOH-promoted cyclization/rearrangementof the resulting acetonyl anthranilate to afford a pseudane intermediate, and afinal selective 3-OH methylation. The synthetic pathway, which was devoid ofprotecting groups, enabled to reach the objective in 11 steps and 18% overallyield. The 1H NMR spectrum of synthetic melovinone was in fullagreement with that reported for the natural product.