Synthesis 2019; 51(22): 4253-4262
DOI: 10.1055/s-0039-1690164
paper
© Georg Thieme Verlag Stuttgart · New York

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

Abel A. Arroyo Aguilar
a  Instituto de Química Rosario (IQUIR, CONICET-UNR) and Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina   Email: larghi@iquir-conicet.gov.ar   Email: kaufman@iquir-conicet.gov.ar
,
Gabriela N. Ledesma
a  Instituto de Química Rosario (IQUIR, CONICET-UNR) and Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina   Email: larghi@iquir-conicet.gov.ar   Email: kaufman@iquir-conicet.gov.ar
,
Bárbara Tirloni
b  Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
,
a  Instituto de Química Rosario (IQUIR, CONICET-UNR) and Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina   Email: larghi@iquir-conicet.gov.ar   Email: kaufman@iquir-conicet.gov.ar
,
a  Instituto de Química Rosario (IQUIR, CONICET-UNR) and Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina   Email: larghi@iquir-conicet.gov.ar   Email: kaufman@iquir-conicet.gov.ar
› Author Affiliations

The authors are indebted to Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (PUE-0006-2016) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT 2014-0445 and PICT 2017-0149) for financial support. AAAA acknowledges CONICET for his Doctoral fellowship. The authors also wish to thank the Agencia Santafesina de Ciencia, Tecnología e Innovación Productiva (ASACTeI) for an institutional grant (AC 2015-0005) to Instituto de Química Rosario (IQUIR) for acquisition of a 400 MHz spectrometer.
Further Information

Publication History

Received: 27 May 2019

Accepted after revision: 26 July 2019

Publication Date:
12 August 2019 (eFirst)

Abstract

The first total synthesis of melovinone, a nonrutaceous 3-methoxy-4-quinolone alkaloid isolated from Melochia tomentosa L., is reported. The target was acquired in a convergent fashion through the Suzuki–Miyaura cross-coupling reaction between an ortho-nitrobenzoic acid acetonyl ester derivative prepared from vanillin and potassium 5-phenyl-1-pentyltrifluoroborate, obtained from β-phenethyl bromide. The coupling was followed by a chemoselective reduction of the nitro group and a microwave-assisted and AcOH-promoted cyclization with rearrangement of the resulting acetonyl anthranilate. This afforded a pseudane intermediate, which was selectively methylated on the 3-OH. The synthetic pathway enabled to reach the objective in 11 steps and 18% overall yield. The 1H NMR spectra of the synthetic and natural product were in full agreement.

Supporting Information

 
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