Synlett 2019; 30(01): 104-108
DOI: 10.1055/s-0037-1611342
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Naphthoic Acids as Potential Anticancer Agents

Lorraine M. Deck*
a  Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA   Email: ldeck@unm.edu
,
Jacob A. Greenberg
a  Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA   Email: ldeck@unm.edu
,
Lisa J. Whalen
a  Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA   Email: ldeck@unm.edu
,
David L. Vander Jagt
b  Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
,
Robert E. Royer
b  Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
› Author Affiliations
Further Information

Publication History

Received: 12 September 2018

Accepted after revision: 02 November 2018

Publication Date:
03 December 2018 (online)

Abstract

As part of ongoing research to investigate structural requirements for lactate dehydrogenase inhibition by highly substituted naphthoic acids, nine new aryl-substituted dihydroxynaphthoic acids were synthesized from three known precursors. Described here are efficient preparations of the 1-naphthoic acid target compounds by using Suzuki coupling reactions, formylations, oxidations, and demethylations. Lactate dehydrogenase inhibition studies conducted with five of the compounds revealed values of the inhibitory constant K i in the low micromolar range.

Supporting Information

 
  • References and Notes

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  • 37 Naphthalenes 12a–e; General Procedure Bromide 11 was combined with the appropriate arylboronic acid in EtOH. K3PO4, TBAB, PdCl2, and H2O were added, and the mixture was stirred at r.t. or heated until the starting material was completely consumed (TLC). The mixture was filtered through a small pad of silica gel, eluting with EtOAc, and the filtrate was washed with 1 M aq NaOH. The organic phase was separated, washed with sat. aq NaCl, then dried (MgSO4) and filtered. The solvent was evaporated to give a crude product, which was purified chromatographically. 2,3-dimethoxy-7-methyl-6-phenyl-1-propylnaphthalene (12a) White crystals; yield: 60%; mp 111–113 °C. 1H NMR (300 MHz, CDCl3): δ = 7.81 (s, 1 H, NaH8), 7.63 (s, 1 H, NaH5), 7.45 (m, 5 H, ArH2, ArH3, ArH4, ArH5, ArH6), 7.07 (s, 1 H, NaH4), 3.98 (s, 3 H, OCH3), 3.94 (s, 3 H, OCH3), 3.12 (t, J = 7.9 Hz, 2 H, NaCH2), 2.46 (s, 3 H, NaCH3), 1.78 (sextet, J = 7.5 Hz, 2 H, C-CH2-C), 1.15 (t, J = 7.3 Hz, 3 H, CH3). 13C NMR (75 MHz, CDCl3): δ = 152.1 (NaC3), 147.1 (NaC2), 142.2, 140.0, 131.6, 130.2, 130.1, 129.5 (ArC3H, ArC5H), 128.2 (ArC2H, ArC6H), 128.0, 127.6, 126.9, 124.7 (NaC1), 105.3 (NaC4H), 61.2 (OCH3), 55.6 (OCH3), 27.9 (NaCH2), 24.2 (CH2), 21.5 (NaCH3), 14.8 (CH3). HRMS (EI): m/z [M + H]+ calcd for C22H25O2: 321.1855; found: 321.1849.