Pergamon 0031-9422(94)00842-6 Phytochemistry, Vol. 39, No. 2, pp. 405-407, 1995 Copyright © 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0031-9422/95 $9.50 + 0.00 ANACARDOSIDE FROM THE SEEDS OF SEMECARPUS ANACARDIUM ROBERTO R. GIL, LONG-ZE LIN, GEOFFREY A. CORDELL, MEDA RAMA KUMAR,* MULLANGI RAMESH,* BOMMINENI MADHAVAREDDY,~ GOTTUMUKKALA KRISHNA MOHAN and ACHANTAVENKATANARASIMHA APPA RAO* Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.; *University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506 000, India (Received in revised form 22 September 1994) Key Word lndex--Semecarpus anacardium; Anacardiaceae; phenolic glycoside; anacardoside; struc- ture determination; 2D NMR techniques. Abstract--From the seeds of Semecarpus anacardium, a new phenolic glucoside, anacardoside, was isolated, and its structure and configuration were elucidated by a combination of NMR techniques as-l-O-fl-D-glucopyranosyl- (1 ~ 6)-fl-D-glucopyranosyloxy-3-hydroxy-5-methylbenzene. INTRODUCTION The fruits of Semecarpus anacardium are claimed to be useful in treating leprosy, rheumatoid arthritis, piles, asthma, cough, sexually transmitted diseases such as syphilis and gonorrhea, and skin diseases such as leuco- derma [1, 2]. The seeds are eaten in certain parts of India and are considered nutritious. Several Ayurvedic prep- arations such as "Bhallataka rasayana", "Amritha bhal- lataki", "Brihat bhallataka lehya" are marketed in India. The fruits of S. anacardium are subjected to a purification process before they are used for Ayurvedic medicines because they are considered to be toxic. Purified fruits are claimed to possess rejuvenating properties, increasing longevity, bringing a glow to the face, a sweetness in tone and improvement in vision [3]. A literature survey revealed that no chemical investiga- tions had been carried out on the seeds of S. anacardium, while the nut shells had been investigated extensively. Anacardic acid [4], semicarpol, bhilawanol [51 mono- lefin I, diolefin II [6, 7], bhilawanol-A and bhilawanol-B [8] have been reported from the vesicant oil of the nuts. The biflavonoid amentoflavone was isolated from the leaves [9], and several other biflavonoids like biflavone A1, A2, B and C [8], tetrahydroamentoflavone, tetrahyd- robustaflavone [9], jeediflavanone, semecarpuflavanone, galluflavanone and anacarduflavone [10-13] were iso- lated from the nut shells. The fruits of S. anacardium have been reported to possess anti-cancer [14-18], anti-in- flammatory, anti-arthritic and anthelmintic activities [19,20]. In this publication we present the isolation, structure elucidation and unambiguous NMR assignments of the ?Present address: AI-AmeenCollege of Pharmacy, Bangalore 560027, India. new phenolic glycoside anacardoside (1) using I H NMR, 13 CNMR (BB and DEPT), COSY, HETCOR, HOHAHA and selective INEPT experiments [21-23]. RESULTS AND DISCUSSION Anacardoside (1) gave a negative reaction with acetic anhydride-H2SO4 for a steroid, but, gave a positive Mollisch test for sugars and FeCla test for phenols. The positive HR-FAB mass spectrum indicated a molecular formula of CI9H2aO12. The tH NMR spectrum (Table 1) showed three broad singlets at 67.15, 6.72 and 6.68, which show long-range coupling to each other in the COSY spectrum. These signals, together with a three- proton singlet at ~2.15, suggested the presence of a 3,5- dihydroxytoluene moiety. We also observed the presence of two anomeric proton resonances at 65.44 (d, J = 7.5 Hz) and 5.05 (d, J = 7.5 Hz), and several carbinol signals between 6 3.7-4.7, indicating the presence of a di- saccharide moiety linked to the aromatic group. The 13CNMR and DEPT spectra of 1 (Table 1), showed the presence of six sp 2 carbon signals (three quaternary and three methine), two anomeric carbon signals, 10 aliphatic carbinol carbon signals (eight methine and two methyl- ene) and one methyl carbon signal. A combination of COSY, NOESY, HOHAHA, HETCOR and selective INEPT experiments led to the unambiguous assignment of all proton and carbon NMR signals. The signals of the anomeric protons were used as starting points in the COSY spectrum, and allowed the assignment of all proton signals. The vicinai coupling constants involving H-I, H-2, H-3, H-4 and H-5 (Table 1) of the sugar moieties indicated the//configuration of the anomeric carbon and permitted identification of both moieties as glucopyranosides. The multiplicities of most of the signals, except for H-Y' and H-4", could be deter- 405