Five new bisbenzylisoquinoline alkaloids were obtained from Stephania subosa. These are (+)-2-norcepharanthine (2), (+)-cepharanthine 2'-p-N-oxide (3), (+) stephasubine (4), (+)-norstephasubine (5), and stephasubimine (6). They are accompanied by the known (+)-cepharanthine (1) which is the main alkaloid. The vine Stephania subosa Forman (Menispermaceae) is a rich source of alkaloids, and the present paper will be concerned with its content of bisbenzylisoquinolines (1,2). Besides the known (+)-cepharanthine (1), which is the major bisbenzylisoquinoline (1), five dimers were obtained, all of which are new and are structurally related to cepharanthine whose detailed 'H-nmr spectrum, confirmed by spin decoupling experiments, has been summarized around expression 1. The first new alkaloid to be characterized was (+)-2-norcepharanthine (2), C36H36N2O6. The secondary amine function was first suggested by a mass spectral molecular weight which was 14 m.u. less than for cepharanthine. A strong molecular peak mlz 592 (78%) was flanked by a base peak mlz 591- pattern often encountered with bisbenzylisoquinolines bearing a secondary amine function (3). Another important peak, mlz 365 (59%), represented the upper half of the molecule. As expected for a bisbenzylisoquinoline incorporating 7-8' and 11-12' ether linkages, the mass spectrum also showed peaks mlz 486 and 485 due to the (M-106)+ and (M-107)+ ions (4). The 'H-nmr spectrum of (+)-2-norcepharanthine, indicated around structure 2, is very close to that for 1. The most obvious difference was the absence of an upfield N-methyl singlet near δ 2.56 and the displacement of the broad H-1 singlet from δ 3.60 in cepharanthine (1) to δ 4.32 in the nor analog. Such a pattern is regularly observed whenever an N-methyltetrahydrobenzylisoquinoline in the monomeric or dimeric form is compared with the corresponding secondary amine (3). The structure of the new alkaloid was then confirmed by its N-methylation using formaldehyde-formic acid to (+)-cepharanthine (1). The second new alkaloid was (+)-cepharanthine 2'-P-N-oxide (3), C37H38N2O7. The mass spectrum showed a small molecular peak mlz 622 (8%), together with a somewhat stronger mlz 620 peak. Such an (M-2)+ ion is often encountered in connection with bisbenzylisoquinoline N-oxides (3). Present also was a strong mlz 606 peak due to net loss of oxygen from the molecular ion. An intense mlz 379 peak represented the top half of the dimer, i.e., rings A, B, A', and B', while an mlz 190 peak corresponded to the doubly charged analog. The 'H-nmr spectrum was again very close to that of cepharanthine as far as the aromatic protons and the aromatic substituents were concerned. A remarkable difference, however, prevailed with the absorptions for the right hand 2'-N-methyl group and the adjoining H-1' which were both shifted downfield. The 2'-N-methyl singlet at δ 3.31 and the H-1' broad singlet at δ 4.63 are characteristic of a trans-relationship between the N-oxide oxygen and H-l' (3). This trans-relationship was further confirmed by an nOe study (5) which showed that irradiation of the δ 3.31 N-methyl singlet resulted in enhancement of the H-1' signal at δ 4.63. The remaining three new bisbenzylisoquinolines are closely related to each other and are all phenolic. (+)-Stephasubine (4), C36H34N2O6, shows a strong mass spectral molecular ion mlz 590 (76%), while mlz 589 is the base peak. The only other important peak is the doubly charged molecular ion mlz 295 (18%). The fact that the upper part of the dimer is not observed in the mass spectrum immediately suggested that an imine or aromatic ring B (or B') was present. This suspicion was reinforced by the uv shift suffered by the dimer upon acidification (6). The 'H-nmr spectrum displayed mutually coupled signals at δ 7.48 and 8.45 (J=5.6 Hz) due to the presence of a substituted pyridine system. Conspicuously present were two doublets at δ 4.52 and 5.37, with a large coupling constant at 13.8 Hz, which represented the two geminal protons of the benzylic methylene adjacent to the pyridine ring. The presence of the H-1 broad singlet upfield at δ 3.56, accompanied by an N-methyl signal at δ 2.51, argued convincingly in favor of placing the pyridine system on the right-hand side of the dimer (3). The structure assignment was then further ascertained by a complete spin decoupling and nOe analysis; the more important of the 'H-nmr values are quoted in the Experimental section. Our fourth new alkaloid is (+)-norstephasubine (5), C35H33N2O6, which showed a mass spectral molecular ion 14 units less than for stephasubine (4), while the general fragmentation pattern was very similar to that for 4. The 'H-nmr spectrum of (+)-norstephasubine (5) is also close to that of 4, except for the absence of an N-methyl signal, and the downfield displacement of H-1 from δ 3.56 to 4.02. This shift is typical for the replacement of a N-methyl group by NH (3). Finally, N-methylation of 5 provided (+)-stephasubine (4). The fifth new alkaloid at our disposal was stephasubimine (6) whose molecular composition, C35H31N2O6, indicated two hydrogens less than in norstephasubine (5). The 'H-nmr spectrum bears distinct similarities to those of dimers 4 and 5. But a noticeable difference is the presence of two extra doublets at δ 3.33 and 3.63 (Jgem=12 Hz), attributable to the benzylic a-methylene protons of a dihydrobenzylisoquinoline. The structure assignment was then complemented by the finding that NaBH4 reduction of 6 provided norstephasubimine (5). Stephasubine (4), norstephasubine (5), and stephasubimine (6) are relatively rare examples of bisbenzylisoquinolines incorporating an aromatic isoquinoline moiety. They all possess a methoxyl at C-6' and a hydroxyl at C-7'. The accompanying cepharanthine (1), norcepharanthine (2), and cepharanthine-2'-P-N-oxide (3) include a tetrahydrobenzylisoquinoline as the right-hand moiety of the dimer. Interestingly, the C-6', C-7' substituent is now a methylenedioxy group.