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Licensed Unlicensed Requires Authentication Published by De Gruyter August 16, 2006

Synthesis of plantamajoside, a bioactive dihydroxyphenylethyl glycoside from Plantago major L.

  • Toshinari Kawada , Yuko Yoneda , Ryuji Asano , Ippei Kan-no and Walther Schmid
From the journal


The first total synthesis of plantamajoside (1), 2-(3′,4′-dihydroxylphenyl)ethyl-4-O-caffeoyl-3-O-(β-D-glucopyranosyl)-β-D-glucopyranoside, which is one of the dihydroxyphenylethyl glycosides (caffeic acid sugar esters), is described. Key intermediate 2, 2-[3′,4′-bis(O-benzyl)phenyl]ethyl 2,6-di-O-acetyl-4-O-[3′,4′-bis(O-benzyl)caffeoyl]-β-D-glucopyranoside was glycosylated with trichloroacetoimidoyl 2,3,4,6-tetra-O-acetyl-α-D-glycopyranoside (3) to afford plantamajoside derivative 4a, 2-[3′,4′-bis(O-benzyl)phenyl]ethyl 2,6-di-O-acetyl-4-O-[3′,4′-bis(O-benzyl)caffeoyl]-3-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-β-D-glucopyranoside, in 39% yield. Plantamajoside derivative 4a was successfully converted into the target compound, plantamajoside (1), through a series of de-protective procedures. 1H- and 13C nuclear magnetic resonance (NMR) spectral data of the synthesized plantamajoside (1) were identical to those of the natural compound.


Corresponding author. Graduate School of Agriculture, Kyoto Prefectural University, Shimogamo, Sakyo-ku, 606-8522 Kyoto, Japan Phone/fax: +81-75-703-5647


Andary, per C., Motte-Florac, M.E., Gargadennec, A., Wylde, R., Heintz, A. (1988) Les esters caféiques du genre Plantago. Identification et valeur chimiotaxinomique. Plantes Médicinales et Phytothérapie22:17–22.Search in Google Scholar

Cometa, F., Tomassini, L., Nicoletti, M. (1993) Phenylpropanoid glycosides: Distribution and pharmacological activity. Fitoterapia LXIV:195–217.Search in Google Scholar

Duynstee, H.I., de Koning, M.C., Ovaa, H., van der Marel, G.A., van Boom, J.H. (1999) Synthesis of verbascoside: a dehydroxyphenylethyl glycoside with diverse bioactivity. Eur. J. Org. Chem.1999:2623–2632.10.1002/(SICI)1099-0690(199910)1999:10<2623::AID-EJOC2623>3.0.CO;2-KSearch in Google Scholar

Felix, A.M., Heimer, E.P., Lambros, T.J., Taougraki, C., Meinenhofer, J. (1978) Rapid removal of protecting groups from peptides by catalytic transfer hydrogenation with 1,4-cyclohexadiene. J. Org. Chem.43:4194–4196.10.1021/jo00415a045Search in Google Scholar

Jiménez, C., Riguera, R. (1994) Phenylethanoid glycosides in plants. Structure and biological activity. Nat. Prod. Rep.11:591–606.Search in Google Scholar

Kawada, T., Asano, R., Hayashida, S., Sakuno, T. (1999) Total synthesis of the phenylpropanoid glycoside, acteoside. J. Org. Chem.64:9268–9271.10.1021/jo9906983Search in Google Scholar

Kawada, T., Asano, R., Makino, K., Sakuno, T. (2000) Synthesis of conandroside: A dihydroxyphenylethyl glycoside from Conandron ramaidioides. Eur. J. Org. Chem.2000:2723–2727.10.1002/1099-0690(200008)2000:15<2723::AID-EJOC2723>3.0.CO;2-YSearch in Google Scholar

Kawada, T., Asano, R., Makino, K., Sakuno, T. (2002) Synthesis of isoacteoside, a dihydroxyphenylethyl glycoside. J. Wood Sci.48:512–515.10.1007/BF00766648Search in Google Scholar

Kochetkov, N.K., Khorlin, A.J., Bochkov, A.F. (1967). A new method of glycosylation. Tetrahedron23:693–707.Search in Google Scholar

Kochetokov, N.K., Bochkov, A.F., Sokolovskaya, T.A., Synyatkova, V.J. (1971) Modifications of the orthoester method of glycosylation. Carbohydr. Res.16:17–27.10.1016/S0008-6215(00)86094-2Search in Google Scholar

Matsumoto, M., Koga, S., Shoyama, Y., Nishioka, I. (1987) Phenolic glycoside composition of leaves and callus cultures of Digitalis purpurea. Phytochemistry26:3225–3227.10.1016/S0031-9422(00)82474-7Search in Google Scholar

Miyase, T., Ishino, M., Akahori, C., Ueno, A., Ohkawa, Y., Tanizawa, H. (1991) Phenylethanoid glycosides from Plantago asiatica. Phytochemistry30:2015–2018.10.1016/0031-9422(91)85059-9Search in Google Scholar

Mølgaard, P. (1986) Population genetics and geographical distribution of caffeic acid esters in leaves of Plantago major in Denmark. J. Ecol.74:1127–1137.10.2307/2260239Search in Google Scholar

Mølgaard, P., Ravn, H. (1988) Evolutionary aspects of caffeoyl ester distribution in dicotyledons. Phytochemistry27:2411–2421.10.1016/0031-9422(88)87005-5Search in Google Scholar

Mølgaard, P., Skjøth, L., Kaufmann, U. (1980) A genetic investigation of the esters of caffeic acid with rhamnose or glucose in leaves of Plantago major. Biochem. Syst. Ecol.8:277–278.10.1016/0305-1978(80)90059-9Search in Google Scholar

Ravn, H., Brimer, L. (1988) Structure and antibacterial activity of plantamajoside, a caffeic acid sugar ester from Plantago major subsp. major. Phytochemistry27:3433–3437.Search in Google Scholar

Ravn, H., Nishibe, S., Sasahara, M., Li, X. (1990) Phenolic compounds from Plantago asiatica. Phytochemistry29:3627–3631.10.1016/0031-9422(90)85289-RSearch in Google Scholar

Schmidt, R.R., Michel, J. (1980) Facile synthesis of α- and β-O-glycosyl imidates: Preparation of glycosides and disaccharides. Angew. Chem. Int. Ed. Engl.19:731–732.10.1002/anie.198007311Search in Google Scholar

Shoyama, Y., Matsumoto, M., Nishioka, I. (1986). Four caffeoyl glycosides form callus tissue of Rehmannia glutinosa. Phytochemistry25:1633–1636.Search in Google Scholar

Published Online: 2006-08-16
Published in Print: 2006-08-01

©2006 by Walter de Gruyter Berlin New York

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