Natural Product Research
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acetate and the precipitates appeared were filtered out. The organic layer was dried over
anhydrous sodium sulphate and evaporated to yield (E)-4-((3-(3,4-dimethoxyphenyl)acryloyl)
oxy)-3-methoxybenzoic acid (4) as a white solid. Yield: 75%, Rf: 0.42, m.p.: 130–1338C, IR
(neat) y (cm21): 1710 (CvO ester), 1720 (CvO acid). 1H NMR (DMSO, d ppm): 12.95 (1H, s,
´
ZCOOH), 7.76 (1H, d, J ¼ 15.9 Hz, b-H), 7.61 (2H, m, HC-600, HC-200), 7.47 (1H, d, J ¼ 1.8 Hz,
HC-500), 7.31 (2H, m, HC-60, HC-20), 7.02 (1H, d, J ¼ 8.4 Hz, HC-50), 6.80 (1H, d, J ¼ 15.90Hz,
a-H), 3.90 (9H, s, ZOMe). 13C NMR (DMSO, d ppm): 170.1 (CvO acid), 164 (CvO ester),
152.14 (b-C), 109.76–151.95 (ArZC), 109.62 (a-C), 55.91–56.14 (ZOMe); elemental
analysis: found: C, 66.59, H, 5.11%; calcd for C19H18O7: C, 63.68; H, 5.06%.
3.1.4. Trilepisumic acid ((E)-4-((3-(3,4-dihydroxyphenyl)acryloyl)oxy)-3-hydroxybenzoic acid)
(1)
(E)-4-((3-(3,4-dimethoxyphenyl)acryloyl)oxy)-3-methoxybenzoic acid (4) (1.2 g, 0.000034 mol)
was refluxed with 33% HBr in glacial acetic acid (6 mL) for 2 h. The reaction mixture was poured
into ice (50 g) and then solid sodium carbonate was added to attain pH 6. The compound was
extracted with ethyl acetate and the solvent was evaporated to afford (E)-4-((3-(3,4-
dihydroxyphenyl)acryloyl)oxy)-3-hydroxybenzoic acid as a silvery crystalline solid. Yield:
75%, Rf: 0.22, m.p.: 130–1338C, IR (neat) y (cm21): 1712 (CvO ester), 1725 (CvO acid), 3450
´
(ZOH). 1H NMR (DMSO, d ppm): 12.95 (1H, s, ZCOOH), 7.78 (1H, d, J ¼ 15.9 Hz, b-H), 7.63
(2H, m, HC-600, HC-200), 7.47 (1H, d, J ¼ 1.8 Hz, HC-500), 7.32 (2H, m, HC-60, HC-20), 7.04 (1H, d,
J ¼ 8.4 Hz, HC-50), 6.82 (1H, d, J ¼ 15.9 Hz, a-H), 5.35 (3H, s, b, ZOH). 13C NMR (DMSO,
d ppm): 170.1 (CvO acid), 164 (CvO ester), 152.14 (b-C), 109.76–151.95 (ArZC), 109.62
(a-C), 55.91–56.14 (ZOMe); MS (70 eV) m/z (%): 296 [M]þz, 251 (34), 177 (16), 147 (100%), 91
(28); elemental analysis: found: C, 60.73, H, 5.26%; calcd for C16H12O7: C, 60.76; H, 4.82%.
4. Conclusions
The first total synthesis of natural antimicrobial metabolite trilepisiumic acid was achieved. The
pivotal steps include the esterification of vanillin with 3,4-dimethoxycinnamic acid followed by
the oxidation of the aldehyde function.
Supplementary material
Supplementary relating to this article is available online, alongside Figures S1–S5.
References
Adisakwattana S, Moonsan P, Anun SY. 2008. Insulin-releasing properties of a series of cinnamic acid derivatives
in vitro and in vivo. J Agric Food Chem. 56:7838–7844.
Ampa R, Ahombo G, Nguimbi E, Diatewa M, Dimo T, Ouamba JM, Abena A. 2013. Evaluation of hypoglycemic,
antihyperglycemic and antidiabetics properties of Trilepisium madagascariense D.C. Leeuwenberg (Moraceae).
J Biotechnol Pharm Res. 4:48–53.
Ango PY, Kapche D, Kuete V, Ngadjui BT, Bezabih M, Abegaz M. 2012. Chemical constituents of Trilepisium
madagascariense (Moraceae) and their antimicrobial activity. Phytochem Lett. 5:524–528.
Alves MJ, Ferreira ICFR, Froufe HJC, Abreu RMV, Martins A, Pintado M. 2013. Antimicrobial activity of phenolic
compounds identified in wild mushrooms, SAR analysis and docking studies. J Appl Microb. 2013. doi:10.1111/
´
Kossakowski J, Krawiecka M, Kuran B, Stefanska J, Wolska I. 2010. Synthesis and preliminary evaluation of the
antimicrobial activity of selected 3-benzofurancarboxylic acid derivatives. Molecules. 15:4737–4749.
Lee SU, Shin CG, Lee CK, Lee YS. 2000. Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of l-chicoric
acid, as a new HIV-1 integrase inhibitors. Eur J Med Chem. 42:1309–1315.