Cyanogenic and non-cyanogenic pyridone glucosides from Acalypha indica (Euphorbiaceae) q Monika Hungeling a , Matthias Lechtenberg a , Frank R. Fronczek b , Adolf Nahrstedt a, * a Institute of Pharmaceutical Biology and Phytochemistry, Westfälische Wilhelms-Universität, Hittorfstraße 56, D-48149 Münster, Germany b Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803-1804, USA article info Article history: Received 16 September 2008 Received in revised form 9 December 2008 Available online 20 January 2009 Keywords: Euphorbiaceae Acalyphoideae Acalypha indica Cyanogenic glucosides Acalyphin Epiacalyphin Noracalyphin Epimeric pairs Corresponding amides Absolute configuration ar-Acalyphidone seco-Acalyphin abstract Seven cyanopyridone derivatives and one corresponding seco compound have been isolated from a meth- anolic extract of the inflorescences and leaves of Acalypha indica L. (Euphorbiaceae). The absolute configuration of the main cyanogenic glucoside acalyphin, ()-(5R,6S)-5-cyano-5-b-D-glucopyranosyl- oxy-6-hydroxy-4-methoxy-1-methyl-2(5,6-dihydro)-pyridone, was deduced from an X-ray crystallo- graphic study. In addition, the 6R-epimer of acalyphin, epiacalyphin, and the corresponding pair of N- demethyl derivatives were isolated. The corresponding amide of acalyphin and a 1 0 ,2 0 -glucosyl-fused epi- acalyphin amide were isolated from air-dried material. Structural elucidation was performed by means of 1 H and 13 C NMR-spectra, chiroptical methods such as CD-spectroscopy and optical rotation. Two further corresponding derivatives, an aromatized compound and an open-chain structure, were isolated from the aqueous phase. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Acalypha indica L. (Euphorbiaceae), Indian copperleaf, is an an- nual tropical weed indigenous to the Indian peninsula, the south- ern districts of China and South Africa (Hagers Handbuch, 1998). The aerial parts and the roots are traditionally used in folk medi- cine as an expectorant, against asthma and pneumonia, as an eme- tic, a purgative and an anthelminthic (Hagers Handbuch, 1998; Siregar, 2001). Various extracts showed antimicrobial and estro- genic activity (Hiremath et al., 1993, 1999). The plant has been de- scribed in homoeopathic pharmacopoeias (Homöopathisches Arzneibuch, 2000). Cyanogenesis of A. indica has been long known (Rimington and Roets, 1937), but it was not before 1982, that the (main) cyanogenic compound was shown to be a cyanopyridone glucoside which was named acalyphin (1)(Fig. 1)(Nahrstedt et al., 1982). Acalyphin (1) represents a new biogenetic type of cya- nogenic glucoside that apparently derives from nicotinic acid metabolism. Cyanogenesis, the ability of living organisms to liberate cyanide upon tissue disruption, is widespread amongst plants. More than 60 different cyanogenic glycosides are known from higher plants and insects (Lechtenberg and Nahrstedt, 1999). Cyanogenic gluco- sides are a-hydroxynitriles which are stabilized by b-linked sugar chains, usually formed of D-glucose. In plants, cyanogenic glyco- sides are usually accompanied by enzymes (b-glucosidase, hydroxynitrile lyase) which finally lead to a liberation of hydrogen cyanide when the tissue is disrupted. Interestingly, the cyanopyridone glucoside acalyphin (1) and similar nitrile structures (without glucosidation) such as ricinine (Waller and Nowacki, 1978), mallorepine (Hikino et al., 1978), ric- inidine (Ganguly, 1970) and nudiflorine (Mukherjee and Chatter- jee, 1966) have been isolated only from members of the subfamily Acalyphoideae (Acalypheae) within the Euphorbiaceae. Nicotinic acid and nicotinic acid amide were shown to be the bio- genetic precursors of ricinine, which indicates a close connection of this type of compound to the pyridine nucleotide (NAD) cycle (Johnson and Waller, 1974). Because the configuration at C-5 and C-6 of the cyanopyridone ring of (1) was not established by Nahrstedt et al. (1982), the aim of this work was to isolate and purify sufficient amount of (1) for 0031-9422/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2008.12.011 * Corresponding author. Tel.: +49 251 8333380; fax: +49 251 8338341. E-mail address: anahrstedt@uni-muenster.de (A. Nahrstedt). Phytochemistry 70 (2009) 270–277 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem