A new monoquaternary bisbenzylisoquinoline alkaloid, (+>2-N-merhylfangchinoline [4], was obtained from the mot of Stepbania tetrandra, the traditional Chinese medicine "fen-fang-ji," along with three known bisbenzylisoquinoline alkaloids 1-3. The traditional Chinese medicine "fen-fang-ji," the root of Stepbania tetrandra S. Moore (Menispermaceae), has been used as an analgesic, diuretic, and detumescent for thousands of years in China. The main alkaloid, tetrandrine 111, has been demonstrated to have broad pharmacological activities including analgesic, antitumor, hypotensive, antimicrobial, and antiarrhythmic effects (1). It also inhibits platelet aggregation and acts as a Ca+' antagonist (1).Our continuing study of the root ofS. tetrandra has yielded (+)-2-N-methylfangchinoline 143 and the known alkaloids (+)-tetrandrine El] and (+) fingchinoline 121, both of which are major components, and (+)-2-Nmethyltetrandrine 131 (2,3).The new monoquaternary bisbenzyliscquinoline (+)-2-N-methylfangchineline 141, C,,H~,O~N,CI-H,O, showed a mass spectral molecular ion at m/z 623, accompanied by the base peak mlz 609 {M - 15 + l]+. The other fragment ion peaks were nearly identical with those of fangchinoline 127. The mass spectrum, in fact, suggested that 4 was similar to 2 except for a mass spectral mol wt which was 15 mu more than for 2. The 'H nmr spectrum of 4 was very close to those of fangchinoline [2] and 2- N-methyltetrandrine 131, with the important difference that there are two quaternary N-methyl singlets (6 3.17 and 6 3.20) in 4, indicating that 4 is a monoquaternary bisbenzylisoquinoline. The absorption for H-1' always appears as a doublet of doublets, whereas that for H-1 assumes the shape of a singlet or a doublet in the 8-7', 11-12' pattern dimer (4). Therefore, for 4, the H-1 absorption that was stronger downfield at 6 4.62 in theshapeofadoublet thanH-1' at 8 4.38 as a doublet of doublets indicated that the quaternary N-methyl groups were adjacent to H-1; i.e., they were located on the left-hand side in the molecule. An nOe analysis further confirmed the site of the quaternary Nmethyl groups. In particular, reciprocating nOe's were observed between H-1' (dd, 6 4.38) and H-8' (s, 6 6.08). Additionally, the H- 1' signal (6 4.38) was enhanced through irradiation of the 2'-N-methyl (s, 6 2.90), and H-10 (d, 6 6.69) was affected by irradiation of H- 1 (d, 6 4.62). All assignments of the substituents were confirmed by spin decoupling experiments and nOe analyses.The cd spectrum of 4 was similar to that of 2, and the N,N,O-methiodide of 4 was characterized by identical ir and cd spectra corresponding to those of the authentic sample, which pointed to the lS, 1's chirality, as in (+)-fangchinoline 121.