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 (online)


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

 
  • References

    • 1a Kapadia GJ, Paul BD, Silverton JV, Fales HM, Sokoloski EA. J. Am. Chem. Soc. 1975; 97: 6814
    • 1b Kapadia GJ, Shukla YN, Basak SP, Fale HM, Sokoloski EA. Phytochemistry 1978; 17: 1444
    • 2a Hoelzel SC. S. M, Vieira ER, Giacomelli SR, Dalcol II, Zanatta N, Morel AF. Phytochemistry 2005; 66: 1163
    • 2b Gressler V, Stüker CZ, Dias G. de O. C, Dalcol II, Burrow RA, Schmidt J, Wessjohann L, Morel AF. Phytochemistry 2008; 69: 994
    • 3a Dias GC. D, Gressler V, Hoenzel SC. S. M, Silva UF, Dalcol II, Morel AF. Phytochemistry 2007; 68: 668
    • 3b Emile A, Waikedre J, Herrenknecht C, Fourneau C, Gantier J.-C, Hnawia E, Cabalion P, Hocquemiller R, Fournet A. Phytother. Res. 2007; 21: 398
    • 4a Jang JY, Le Dang Q, Choi YH, Choi GJ, Jang KS, Cha B, Luu NH, Kim JC. J. Agric. Food Chem. 2015; 63: 68
    • 4b Jang JY, Le Dang Q, Choi YH, Choi GJ, Jang KS, Cha B, Luu NH, Kim JC. J. Agric. Food Chem. 2015; 63: 3803
    • 4c Jang JY, Dang QL, Choi GJ, Park HW, Kim J.-C. Pest. Manag. Sci. 2019; 75: 2264
    • 4d Wang GC, Li T, Wei Y.-R, Zhang Y.-B, Li Y.-L, Sze SC. W, Ye WC. Fitoterapia 2012; 83: 1643
    • 4e Jadulco RC, Pond CD, Van Wagoner RM, Koch M, Gideon OG, Matainaho TK, Piskaut P, Barrows LR. J. Nat. Prod. 2014; 77: 183
    • 5a Cretton S, Breant L, Pourrez L, Ambuehl C, Marcourt L, Ebrahimi SN, Hamburger M, Perozzo R, Karimou S, Kaiser M, Cuendet M, Christen P. J. Nat. Prod. 2014; 77: 2304
    • 5b Cretton S, Dorsaz S, Azzollini A, Favre-Godal Q, Marcourt L, Ebrahimi SN, Voinesco F, Michellod E, Sanglard D, Gindro K, Wolfender J.-L, Cuendet M, Christen P. J. Nat. Prod. 2016; 79: 300
    • 6a Soekamto NH, Liong S, Fauziah S, Wahid I, Firdaus Taba P, Ahmad F. J. Phys.: Conf. Ser. 2018; 979: 012017
    • 6b Cretton S, Bréant L, Pourrez L, Ambuehl C, Perozzo R, Marcourt L, Kaiser M, Cuendet M, Christen P. Fitoterapia 2015; 105: 55
    • 6c Simoben CV, Ntie-Kang F, Akone SH, Sippl W. Nat. Prod. Bioprospect. 2018; 8: 151
    • 6d Monteillier A, Cretton S, Ciclet O, Marcourt L, Ebrahimi SN, Christen P, Cuendet M. J. Ethnopharmacol. 2017; 203: 214
    • 7a Petit C, Ceccarelli M, Cretton S, Houriet J, Skalicka-Woźniak K, Christen P, Carrupt P.-A, Goracci L, Wolfender J.-L. Planta Med. 2017; 83: 718
    • 7b Petit C, Bujard A, Skalicka-Woźniak K, Cretton S, Houriet J, Christen P, Carrupt P.-A, Wolfender J.-L. Planta Med. 2016; 82: 424
    • 7c Zongo F, Ribuot C, Boumendjel A, Guissou I. J. Ethnopharmacol. 2013; 148: 14
    • 8a Khamphaya W., Ngernmeesri P.; Toward the total synthesis of anti-HIV waltherione C.; Proceedings of the 2016 Pure and Applied Chemistry International Conference (PACCON 2016), Bangkok, Thailand, February 9–11, 2016.; SYN-1113.
    • 8b Mäkinen ME, Mallik R, Siitonen JH, Kärki K, Pihko PM. Synlett 2017; 28: 1209
    • 8c Arroyo Aguilar AA, Bolívar Avila SJ, Kaufman TS, Larghi EL. Org. Lett. 2018; 20: 5058
    • 8d Zdorichenko V, Paumier R, Whitmarsh-Everiss T, Roe M, Cox B. Chem. Eur. J. 2019; 25: 1286
    • 9a Cortés I, Borini Etichetti CM, Girardini JE, Bracca AB. J, Kaufman TS. Synthesis 2019; 51: 433
    • 9b Pergomet JL, Bracca AB. J, Kaufman TS. Org. Biomol. Chem. 2017; 15: 7040
    • 9c Méndez MV, Heredia DA, Larghi EL, Bracca AB. J, Kaufman TS. RSC Adv. 2017; 7: 28298
    • 9d Pergomet JL, Larghi EL, Kaufman TS, Bracca AB. J. RSC Adv. 2017; 7: 5242
    • 9e Simonetti SO, Larghi EL, Bracca AB. J, Kaufman TS. Org. Biomol. Chem. 2012; 10: 4124
    • 10a Pergomet JL, Di Liberto MG, Derita MG, Bracca AB. J, Kaufman TS. Fitoterapia 2018; 125: 98
    • 10b Simonetti SO, Larghi EL, Kaufman TS. Org. Biomol. Chem. 2016; 14: 2625
    • 10c Pergomet JL, Kaufman TS, Bracca AB. J. Helv. Chim. Acta 2016; 99: 398
    • 10d Heredia DA, Larghi EL, Kaufman TS. Eur. J. Org. Chem. 2016; 1397
  • 11 Hartz R. In Name Reactions in Heterocyclic Chemistry II . Li JJ, Corey EJ. Wiley; New York: 2011
  • 12 Otto N, Ferenc D, Opatz T. J. Org. Chem. 2017; 82: 1205
    • 13a Chen H, Long H, Cui X, Zhou J, Xu M, Yuan G. J. Am. Chem. Soc. 2014; 136: 2583
    • 13b Takaya D, Yamashita A, Kamijo K, Gomi J, Ito M, Maekawa S, Enomoto N, Sakamoto N, Watanabe Y, Arai R, Umeyama H, Honma T, Matsumoto T, Yokoyama S. Bioorg. Med. Chem. 2011; 19: 6892
    • 14a Raiford LC, Stoesser WC. J. Am. Chem. Soc. 1928; 50: 2556
    • 14b Hazlet SE, Lehman JJr. J. Org. Chem. 1962; 27: 2139
    • 14c Sakamoto T, Miura N, Kondo Y, Yamanaka H. Chem. Pharm. Bull. 1986; 34: 2760
    • 14d Raiford LC, Floyd DE. J. Org. Chem. 1943; 8: 358
  • 15 CCDC 1911796 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures
    • 17a Coulter MM, Kou KG. M, Galligan B, Dong VM. J. Am. Chem. Soc. 2010; 132: 16330
    • 17b Chen C, Dugan TR, Brennessel WW, Weix DJ, Holland PL. J. Am. Chem. Soc. 2014; 136: 945
    • 18a Djellal A, Djerourou A. Phosphorus, Sulfur Silicon Relat. Elem. 2004; 179: 1123
    • 18b Adams J, Behnke ML, Castro AC, Evans CA, Grenier L, Grogan MJ, Liu T, Snyder DA, Tibbitts T. PCT Int. Appl WO 2008063300, 2008 ; Chem. Abstr. 2008, 149, 10119
    • 19a Molander G, Ito T. Org. Lett. 2001; 3: 393
    • 19b Vedejs E, Fields SC, Hayashi R, Hitchcock SR, Powell DR, Schrimpf MR. J. Am. Chem. Soc. 1999; 121: 2460
  • 20 Cleaver L, Nimgirawath S, Ritchie E, Taylor WC. Aust. J. Chem. 1976; 29: 2003
    • 21a Khurana JM, Gogia A. Org. Prep. Proced. Int. 2009; 29: 1
    • 21b Seltzman HH, Berrang SD. Tetrahedron Lett. 1993; 34: 3083
    • 22a Hradil P, Hlaváč J, Lemr K. J. Heterocycl. Chem. 1999; 36: 141
    • 22b Hradil P, Grepl M, Hlavác J, Soural M, Malon M, Bertolasi V. J. Org. Chem. 2006; 71: 819
    • 22c Hodgkinson JT, Galloway WR. J. D, Saraf S, Baxendale IR, Ley SV, Ladlow M, Welch M, Spring DR. Org. Biomol. Chem. 2011; 9: 57
    • 23a Marco-Contelles J, Pérez-Mayoral E, Samadi A, Carreiras MC, Soriano E. Chem. Rev. 2009; 109: 2652
    • 23b Hartz R. In Name Reactions in Heterocyclic Chemistry II . Li JJ, Corey EJ. Wiley; New York: 2011: 376-384
  • 24 Maurer CK, Steinbach A, Hartmann RW. J. Pharm. Biomed. Anal. 2013; 86: 127
  • 25 Morel AF, Larghi EL, Manke Selvero M. Synlett 2005; 2755
    • 26a Simonetti SO, Larghi EL, Kaufman TS. Org. Biomol. Chem. 2014; 12: 3735
    • 26b Su W, Urgaonkar S, Verkade JG. Org. Lett. 2004; 6: 1421
    • 26c Stille JK, Groh BL. J. Am. Chem. Soc. 1987; 109: 813
    • 26d Echavarren AM, Stille JK. J. Am. Chem. Soc. 1987; 109: 5478
    • 27a Bennett CJ, Caldwell ST, McPhail DB, Morrice PC, Duthie GG, Hartley RC. Bioorg. Med. Chem. 2004; 12: 2079
    • 27b Lo M, Mahajan D, Wytko JA, Boudon C, Weiss J. Org. Lett. 2009; 11: 2487
    • 27c McLane RD, Le Cozannet-Laidin L, Boyle MS, Lanzillotta L, Taylor ZL, Anthony SR, Tranter M, Onorato AJ. Bioorg. Med. Chem. Lett. 2018; 28: 334
    • 28a Higman CS, Plais L, Fogg DE. ChemCatChem 2013; 5: 3548
    • 28b Hong SH, Sanders DP, Lee CW, Grubbs RH. J. Am. Chem. Soc. 2005; 127: 17160
    • 28c Bilel H, Hamdi N, Zagrouba F, Fischmeister C, Bruneau C. RSC Adv. 2012; 2: 9584
  • 30 Armarego WL. F, Chai CL. L. Purification of Laboratory Chemicals, 5th ed. Butterworth-Heinemann; Oxford: 2003
  • 31 Wagner H, Bladt S, Rickl V. Drug Analysis: A Thin Layer Chromatography Atlas, 2nd ed. Springer; Heidelberg: 2009: 360
  • 32 Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
    • 33a Adepu R, Prasad B, Ashfaq MA, Ehtesham NZ, Pal M. RSC Adv. 2014; 4: 49324
    • 33b Martin P. Helv. Chim. Acta 1989; 72: 1554
  • 34 Wang C, Wang T, Huang L, Hou Y, Lu W, He H. Arab. J. Chem. 2016; 9: 882