Roemeria refracta of Turkish origin produces the new benzyltetrahydroisoquinoline alkaloids (+)-roefractine [1] and (+)-pseudolaudanine [2], together with the known (+)-roemecarine [3] and (-)-armepavine. As part of an ongoing study of the alkaloids of Turkish Roemeria (Papaveraceae) species, we had occasion to investigate the content of a fraction of Roemeria refracta DC. obtained by elution of the alkaloids through a Si gel column using 5% MeOH in CHCl₃. This fraction was further purified by tlc to yield two new benzyltetrahydroisoquinoline (BTHI) alkaloids, (+)-roefractine [1] and (+)-pseudolaudanine [2]. The uv spectrum of (+)-roefractine [1], C₁₉H₂₁NO₃, displayed a maximum at 285 nm, suggesting that the molecule incorporated a tetrahydroisoquinoline system. Furthermore, a bathochromic shift upon addition of base made it probable that a phenolic function was present. The ¹H-nmr spectrum (360 MHz, CDCl₃), outlined around structure 1, displayed an AA'BB' system at δ 6.82 and 7.02 reminiscent of a coclaurine-type base. Three-proton singlets at δ 3.56 and 3.79 represented two methoxyl groups. It is well known that 7-MeO in coclaurine-type alkaloids resonates at δ 3.51-3.55 (1). Presently, the upfield shift at δ 3.56 was in line with a methoxyl at C-7. In general, in 6-hydroxy-7-methoxy BTHIs, H-8 resonates between δ 5.8 and 6.0, whereas the range is from δ 6.3 to 6.4 when the positions of these substituents are reversed. The chemical shift of the H-8 singlet of 1 fell at δ 5.95, supporting the assumption that we were indeed dealing with a 6-hydroxy-7-methoxy substitution pattern. In the eims, the abundance of the molecular ion m/z 313 was less than 1%, while the base peak, m/z 192, corresponded to the N-methylisoquinolinium cation with one methoxyl and one hydroxyl substituent. An additional prominent peak, m/z 177 (24%), was formed by loss of a methyl radical from the base ion. A cims in CH₄, however, clearly showed m/z 313 as the molecular ion. In order to ascertain the positions of the substituents, a partial ¹H-nmr nOe experiment was carried out. Irradiation of the δ 5.95 and then the δ 3.56 peaks showed strong reversible nOe's. On the other hand, irradiation of the other aromatic proton singlet (δ 6.62) effected only enhancement of H-4 (δ 2.70-2.88). Irradiation of the other methoxyl singlet (δ 3.79) enhanced the aromatic doublet at δ 6.82, thus confirming the position of this methoxyl at C-4'. The cd curve of (+)-roefractine [1] displayed prominent maxima at 235 and 290 nm and was almost identical with that reported for (+)-laudanosine possessing the C-1 S configuration (2). It follows that (+)-roefractine [1] also incorporates the S configuration at its chiral center. Final proof of structure was obtained through CH₂N₂ O-methylation of 1, which gave rise to (+)-O-methylarmepavine, identical (nmr, mass, cd, tlc) with an authentic sample in our possession, as well as with literature values (3). (+)-Roefractine [1] had been previously obtained as a product of the lithium in liquid NH₃ cleavage of the bisbenzylisoquinoline (+)-isotetrandrine (1,4). The present study is the first report of the natural Occurrence of this BTHI. The ¹H-nmr spectrum of our second alkaloid, (+)-pseudolaudanine [2], C₂₀H₂₃NO₄, showed the chemical shifts of the aromatic singlets (δ 5.97 and 6.62) to be very close to those of (+)-roefractine [1], suggesting the identical substitution pattern on ring A. However, the remaining three aromatic protons displayed an ABX pattern, pointing to C-3', -4' substitution on ring C. Three methoxyl resonances were clearly in evidence at δ 3.56, 3.80, and 3.86, the former attributable to 7-MeO (1). Once again, a partial nmr nOe experiment was performed to define the substitution on ring A and to assign the chemical shifts of the methoxyl groups. The H-8 singlet at δ 5.97 and the upfield 7-MeO singlet at 3.56 displayed reversible nOe's. Irradiation of H-8 also enhanced the H-1 signal (δ 3.70). Saturation of the second aromatic singlet (δ 6.62) only caused enhancement of the H-4 benzylic protons (δ 2.70-2.88). Finally, irradiation of the 3'-MeO signal (δ 3.80) affected the meta-coupled H-2' doublet (δ 6.59), whereas irradiation of 4'-MeO (δ 3.86) resulted in enhancement of the ortho-coupled H-5' (δ 6.78). The eims of 2 furnished only a very small molecular ion m/z 343 (0.1%). The base peak, m/z 192, corresponded to the same isoquinolinium fragment observed in the mass spectrum of (+)-roefractine [1]. A cims in isobutane showed m/z 343 as the molecular ion, thus confirming the proposed structure 2. The uv maximum at 282 nm as well as the distinct bathochromic shift in alkali gave added support to the structural assignment. The cd spectrum of 2 was generally similar to that of 1, with maxima at 213, 238, and 288 nm. It follows, therefore, that alkaloid 2 also has the C-1 S configuration. O-Methylation of (+)-pseudolaudanine [2] gave (+)-laudanosine, identified by its spectra (nmr, mass, cd) as well as by comparison with an authentic sample. Synthetic pseudolaudanine had been obtained by Burger (5) more than sixty years ago as one of the four partial O-demethylation products of racemic laudanosine, but the natural Occurrence of (+)-pseudolaudanine [2] is reported for the first time in the present study. It should also be mentioned that a quaternary N-metho salt of pseudolaudanine had been isolated as its styphnate from Fugara mayu (Rutaceae) under the name N-methylpseudolaudanine, but no indication of its optical activity was given (6). At a later date, the dextrorotatory methiodide salt of pseudolaudanine was obtained from Papaver pseudo-orientale (Papaveraceae) and was assigned the name (+)-pseudorine (7). The alkaloidal fraction presently under investigation contained, in addition to the above two new alkaloids, two known BTHI bases, namely (+)-roemecarine [3] and (-)-armepavine. The former is a 4-hydroxylated BTHI originally isolated from Roemeria carica (8,9). Its reisolation from R. refracta suggests that this alkaloid may be a common element of the alkaloidal profile of this genus. Perusal of the order of substitution in structures 1-3 also suggests that the 6-hydroxy-7-methoxy pattern for the Roemeria BTHI may be fairly common. Additionally, the trioxygenated BTHI of Roemeria species may belong to either the S or the R configurations, as exemplified by (-)-armepavine and by (+)-roefractine [1].