Anticancer diarylheptanoid glycosides from the inner bark of Betula papyrifera Vakhtang Mshvildadze, Jean Legault, Serge Lavoie, Charles Gauthier, Andre ´ Pichette * Laboratoire d’Analyse et de Se ´paration des Essences Ve ´ge ´tales, De ´partement des Sciences Fondamentales, Universite ´ du Que ´bec a ` Chicoutimi, 555 boul. Universite ´, Chicoutimi, Que ´bec, Canada G7H 2B1 Received 19 March 2007; received in revised form 19 April 2007 Available online 27 June 2007 Abstract Phytochemical investigations of the MeOH extract of Betula papyrifera inner bark led to the isolation of ten phenolic compounds of the following types: diarylheptanoid glycosides (1–4), a diarylheptanoid (5), a lignan (6), flavonoids (7–8) and chavicol glycosides (9–10). Among them, the diarylheptanoid glycoside, (S)-1,7-bis-(4-hydroxyphenyl)-heptan-3-one-5-O-a-L-arabinofuranosyl-(1 ! 6)-b-D-gluco- pyranoside, papyriferoside A (1), was isolated and its structure was determined on the basis of 1D and 2D NMR, HPLC-MS, as well as high resolution mass spectroscopic data. Platyphylloside (4) exerted the strongest cytotoxic activity of all isolated compounds with IC 50 values ranging from 10.3 to 13.8 lM. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Betula papyrifera; Betulaceae; Birch; Bark; Diarylheptanoid; Chavicol; Glycoside; NMR; Cytotoxic; Anticancer 1. Introduction White birch, commonly named ‘‘paper birch’’, is widely distributed in the boreal forest of North America (Marie- Victorin, 2002). The important industrial exploitation of birch yields a high amount of waste bark, which prompted us to investigate this residue for possible natural bioactive compounds. Pentacyclic triterpenoids, mostly of the lupane and oleanane types, were isolated from the outer bark of various white birch species including Betula papyrifera Marsh. (Betulaceae) (Ekman, 1983; O’Connell et al., 1988; Cole et al., 1991; Hua et al., 1991; Fuchino et al., 1996a,b, 1998; Habiyaremye et al., 2002; Cichewicz and Kouzi, 2004; Gauthier et al., 2006). For example, betulinic acid, a promising anticancer agent (Cichewicz and Kouzi, 2004), is found in appreciable quantities (>1%) in the bark of B. papyrifera (O’Connell et al., 1988). Previous reports on the phytochemical investigations of the inner bark of different Betula species described the isolation of arylbuta- noids, diarylheptanoids, lignans and phenolic glycosides (Smite et al., 1993, 1995; Pan and Lundgren, 1994; Frank et al., 1996, 1997). High antioxidant, cytotoxic, antitumor and antiviral activities for several of these natural com- pounds were reported (Baglin et al., 2003a,b; Setzer and Setzer, 2003; Cichewicz and Kouzi, 2004; Ju et al., 2004). We present in this work the isolation and identification of ten phenolic compounds isolated for the first time from Betula papyrifera. To the best of our knowledge, (S)-1,7- bis-(4-hydroxyphenyl)-heptan-3-one-5-O-a-L-arabinofur- anosyl-(1 ! 6)-b-D-glucopyranoside, papyriferoside A (1), is a new diarylheptanoid glycoside not reported until now. 5-O-b-D-apiofuranosyl-(1 ! 2)-b-D-glucopyranosyl- 1,7-bis-(4-hydroxyphenyl)-heptan-3-one (2)(Smite et al., 1993), aceroside VII (3) (Fuchino et al., 1996a), platyphylloside (4)(Smite et al., 1993), 1,7-bis-(4-hydroxy- phenyl)-4-hepten-3-one (5)(Fuchino et al., 1996), ()-lyo- niresinol 3-O-b-D-xylopyranoside (6)(Smite et al., 1995), (+)-catechin (7)(Hua et al., 1991) and (+)-catechin-7-O- b-D-xylopyranoside (8)(Fuchino et al., 1998) were previ- 0031-9422/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2007.05.018 * Corresponding author. Tel.: +1 418 545 5011; fax: +1 418 545 5012. E-mail address: andre_pichette@uqac.ca (A. Pichette). www.elsevier.com/locate/phytochem Phytochemistry 68 (2007) 2531–2536 PHYTOCHEMISTRY