Quinolizidine Alkaloids from Sophora alopecuroides Atta-ur-Rahman,* M. Iqbal Choudhary,* Khalid Parvez, ² Aftab Ahmed, ² Farzana Akhtar, ² M. Nur-e-Alam, ² and Naeem M. Hassan International Center for Chemical Sciences, H.E.J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan, and Department of Chemistry, University of Baluchistan, Quetta, Pakistan Received July 14, 1999 A new matrine-type alkaloid, 7R-hydroxysophoramine (1), was isolated from the aerial parts of Sophora alopecuroides together with eight known alkaloids, 12-hydroxysophocarpine (2), sophoramine (3), 14- hydroxymatrine, matrine, sophoridine, sophocarpine, adenocarpine, and baptifoline. The structures of compounds 1-3 were confirmed through single-crystal X-ray diffraction analysis. The plant Sophora alopecuroides L. (Leguminosae) is widely distributed over a large area of the Asian continent. 1 Biological studies on the constituents found in this plant have been performed in terms of potential sedative, central nervous system depressant, analgesic, hypother- mic, 2 antitussive, 3 anticancer, 4,5 nematocidal, 6 antispas- modic, 7 antipyretic, 8 cardiotonic, 9 hypoglycemic, l0 and many other pharmacological activities. 11-14 In this communica- tion, studies on S. alopecuroides have led to the isolation of a new alkaloid (1) and several known alkaloids. Among these alkaloids 12-hydroxysophocarpine (2), 14-hydroxy- matrine, and adenocarpine have not been isolated previ- ously from this species. Results and Discussion Aerial parts of S. alopecuroides were collected from the Baluchistan province of Pakistan and extracted with 80% ethanol. The extract was subjected to solvent-solvent extraction and repeated column chromatography on Si gel to obtain the new alkaloid, 7R-hydroxysophoramine (1) together with seven known alkaloids: 12-hydroxysopho- carpine 15 (2), sophoramine 16,17 (3), 14-hydroxymatrine, 18 adenocarpine, 19 matrine, 20 sophoridine, 21,22 sophocarpine 4,23 and baptifoline. The structures of the compounds were determined unambiguously using either X-ray diffraction technique or 1D and 2D 1 H and 13 C NMR experiments in conjunction with the analysis of mass spectral and other spectroscopic data. The molecular formula of the new alkaloid 1 was determined by HREIMS to be C 15 H 20 N 2 O 2 (m/z 260.1511). Its IR spectrum (CHCl 3 ) showed absorption bands of hydroxyl (ν max 3236 cm -1 ), R,-unsaturated lactam (ν max 1540 cm -1 for CdC and ν max 1660 cm -1 for CdO), and trans-quinolizidine (ν max 2928, 2855, 2793, and 2735 cm -1 ) functionalities. 24 The EIMS showed a peak at m/z 243 corresponding to [M - OH] + . The 1 H NMR spectrum (CDC1 3 ) was very similar to that of sophoramine (3). The downfield protons resonating at δ 7.13 (dd, J 13,14 ) 8.9 Hz, J 13,12 ) 7.2 Hz), 6.40 (dd, J 12,13 ) 7.2 Hz, J 12,14 ) 1.2 Hz), and 6.19 (dd, J 14,13 ) 8.9 Hz, J 14,12 ) 1.2 Hz) were assigned to H-13, H-12, and H-14, respectively. Two other downfield signals at δ 3.99 (dd, J 17,17R ) 14.2 Hz, J 17,5 ) 7.0 Hz) and 3.61 (dd, J 17R,17 ) 14.2 Hz, J 17R,5 ) 13.0 Hz) could be assigned to H-17and H-17R, respectively. The lack of any other downfield methine signal indicated that alkaloid 1 might contain a hydroxyl group on a quaternary carbon. The 13 C NMR spectra (BB and DEPT) of 1 showed 15 carbon signals with seven methylene, five methine, and three quaternary carbons. The chemical shift of a quater- nary carbon (δ 69.3) also indicated the presence of a tertiary hydroxyl group. In the HMBC spectrum (Figure 1), the proton resonating at δ 6.19 (H-14) showed a long- range heteronuclear connectivity with C-15 (δ 163.7), while H-13 (δ 7.13) showed HMBC connectivities with C-15 (δ 163.7), C-14 (δ 118.1), C-12 (δ 104.1), and C-11 (δ 148.5). H-12, resonating at δ 6.40, exhibited HMBC interactions with C-14, C-11, and C-7 (δ 69.3), whereas H-17(δ 3.99) was coupled with C-15, C-11, C-6 (δ 66.5), and C-5 (δ 25.6). These results suggested that the new alkaloid 1 is of the matrine-type, in which a hydroxyl group is present at the ring junction (i.e., C-7). The structure of 1 was established unambiguously as 7R-hydroxysophoramine by X-ray dif- fraction methods. A suitable crystal that formed in the orthorhombic space group, P2 1 2 1 2 1 , was selected for the experiment. Accurate lattice constants were a ) 7.836(2), b ) 12.021(2), and c ) 14.342(8) Å, with four independent molecules in the asymmetric unit. All unique diffraction * Authors to whom correspondence should be addressed. Tel.: +92-21- 499-0007. Fax: +92-21-496-3373 or 496-3124. E-mail: hejric@digicom.net.pk. ² University of Karachi. University of Baluchistan. Figure 1. HMBC correlations in compound 1. 190 J. Nat. Prod. 2000, 63, 190-192 10.1021/np990351v CCC: $19.00 © 2000 American Chemical Society and American Society of Pharmacognosy Published on Web 01/19/2000