α‑Glucosidase Inhibitory Hydrolyzable Tannins from Eugenia jambolana Seeds Raed Omar, Liya Li, Tao Yuan, and Navindra P. Seeram* Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, United States * S Supporting Information ABSTRACT: Three new hydrolyzable tannins including two gallotannins, jamutannins A (1) and B (2), and an ellagitannin, iso-oenothein C (3), along with eight known phenolic compounds were isolated from the seeds of Eugenia jambolana fruit. The structures were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for α-glucosidase inhibitory effects compared to the clinical drug acarbose. T he edible fruit of the native Indian medicinal plant Eugenia jambolana Lam. (syn. Syzygium cuminii Skeels; Eugenia cuminii Druce) is commonly known as Jamun. 1 The seeds of the Jamun fruit is widely regarded in the Indian traditional system of medicine, Ayurveda, for regulating blood glucose levels and treating diabetes. 2 Laboratory studies have revealed that Jamun seed extracts inhibit the activities of the carbohydrate hydrolyzing enzymes α-amylase and α-glucosi- dase. 3-5 Animal and human clinical studies also support the antidiabetic effects of Jamun seeds. 6-9 Furthermore, botanical dietary supplements containing Jamun seed extracts are commercially available to consumers as natural approaches for lowering blood glucose (for example, Madeglucyl from Indena; http://www.indena.com/index.php/madeglucyl-the- natural-way-to-maintain-healthy-blood-sugar-levels.html). De- spite all of the aforementioned facts, there is limited knowledge on the chemical constituents of Jamun seeds, prompting the initiation of this research project. Herein, the isolation and structure elucidation of three new hydrolyzable tannins (1-3) along with the purification of eight known phenolic compounds from Jamun seeds are reported. The isolates were evaluated for their α-glucosidase inhibitory effects compared to the clinical drug acarbose. Compound 1, a colorless, viscous liquid, was assigned the molecular formula C 25 H 32 O 13 based on HRESIMS data at m/z 539.1769 [M - H] - (calcd for C 25 H 31 O 13 , 539.1765). The IR absorptions revealed the presence of hydroxy (3500-3020 cm -1 ), ester carbonyl (1722 cm -1 ), ketocarbonyl (1714 cm -1 ), COOH (1700 cm -1 ), and aromatic (1618 and 1516 cm -1 ) functionalities. The 1 H NMR spectrum (Table 1) showed a two-proton singlet at δ H 7.06 (H-2″,6″), suggesting the presence of a galloyl group, which was confirmed by the 13 C NMR data (Table 1) and HMBC correlations. Two olefinic protons at δ H 5.28 (1H, dd, J = 12.6, 10.3 Hz, H-3) and 5.52 (1H, ddd, J = 10.3, 8.6, 6.5 Hz, H-4) revealed the presence of a cis double bond. The 13 C NMR data of 1 (Table 1) showed 25 carbons, including one methyl, six methylenes, and 12 methines along with six quaternary carbons [including one ester carbonyl at δ C 166.6 (C-7″), one ketocarbonyl at δ C 219.4 (C-2′), and one carboxylic group at δ C 174.8 (C-7′)]. The NMR data suggested the presence of a β-glucopyranose moiety for which the anomeric proton resonated at δ H 4.27 (1H, d, J = 8.0 Hz, H-1″′). Detailed analysis of the 1D and 2D NMR ( 1 H- 1 H COSY, HSQC, HMBC) data allowed for the construction of the structure of compound 1. All of the proton signals were assigned to the corresponding carbons through direct 1 H and 13 C correlations in the HSQC spectrum. From the 1 H- 1 H COSY analysis, two substructures (drawn with bold bonds in Figure 2) were established. In the HMBC spectrum, the correlations from H-1′, H-3′, H-4′a(δ H 2.15) and H-5′ to the ketocarbonyl (C-2′) indicated the presence of a cyclo- pentanone structure. Furthermore, the correlation from H-6′ to C-7′, C-5′, and C-4′ suggested that a carboxymethyl group was attached to the cyclopentanone moiety at C-5′. The aforementioned NMR data allowed for the determination of the aglycone of 1 as 5-(5-carboxymethyl-2-oxocyclopentyl)-3Z- 2-pentenol. The HMBC correlations from H 2 -6″′ to C-7″ and from H-1″′ to C-2 revealed that the galloyl group was attached to the glucopyranose moiety at C-6″′ and that the 2-pentenol moiety was attached to C-1″′. The relative configuration of C- 1′ and C-5′ was identified as trans based on comparison of the chemical shifts of H-1′ and H-5′ (δ H 1.50 and 2.22, respectively) to those of the corresponding protons of the previously reported compound (1′R,5′R)-5-(5-carboxymethyl- 2-oxocyclopentyl)-3 Z -pentenyl- β - D -(6- O -galloyl)- glucopyranoside. 10 Compound 2, a colorless liquid, was identified as an epimer of compound 1 with an identical molecular formula of C 25 H 32 O 13 as determined by HRESIMS at m/z 539.1786 [M - H] - (calcd for C 25 H 31 O 13 , 539.1765). The NMR data of Received: June 14, 2012 Published: August 6, 2012 Note pubs.acs.org/jnp © 2012 American Chemical Society and American Society of Pharmacognosy 1505 dx.doi.org/10.1021/np300417q | J. Nat. Prod. 2012, 75, 1505-1509