Reframine

Amurensinine V-metho salt (31) Reframine Al-metho salt (32) (= remrefine, roetmefine) C21H24NO4 + C21H24NO4+ 354 0—CH2—0 354 OMe OMe OMe OMe 0—CH2—0... 

The isopavine bases, ( )-amurensinine (25) (81,135), ( )-0-meth-ylthalisopavine (26) (136), ( )-reframidine (27) (77), and ( )-reffamine (28) (77) were synthesized by the above-mentioned classical route, where deoxy-benzoins were utilized as starting materials. In some cases, some modification to the method has been introduced, particularly involving the formation of the requisite benzylaminoacetals (77,110). The synthesis of ( )-thalisopavine (30) was undertaken along parallel lines to confirm the structure of the naturally occurring base (53). Moreover, both ( )-reframoline (29) and its positional isomer ( )- 146 were synthesized in an attempt to establish the position of the phenolic hydroxyl (110). The synthesis of ( )-reframine (28) from the properly substituted deoxybenzoin 94 has been outlined in Scheme 16 as a typical example (77). 

A facile acid-catalyzed double cyclization of A,A-dibenzylaminoacetaldehyde dialkyl acetals of type 125 has been known to generate l-azadibenzo[c,/]bicy-clo[3.3.1]nona[3,6]dienes 126 in high yields 120,121,147). A novel and convenient synthesis of ( )-amurensinine (25) and ( )-reframine (28) (Scheme 25) proceeds from the quaternary salt 127, where proper choice of base and reaction... 

Methylation of the ( )-isopavines 224 and 225 with diazomethane produced ( )-(9-methylthalisopavine (226) and ( )-reframine (227) (69). More recently, Meyers et al. (71) reported that (-)-isopavines 224 and 225 and (-)-O-methylthalisopavine (226) may be prepared starting from the corresponding (+)-tetrahydroisoquinolin-6-ols 77 and 78 by similar methodology. 

Immediately after publication of the paper 429) on the constitution of amurensine and amurensinine, Yunusov et al. 550) reported the isopavine structure for the alkaloid remrefine which was previously isolated by him. A short time later, Slavik et al. 483) isolated three other compounds (Table XII), reframine, reframidine, and reframoline, whose constitution was determined by correlation of the UV and IR spectra of the products of Hofmann degradation. From the optical rotatory data it appears that all the alkaloids isolated thus far have the same configuration at the C-1 and the C-4 atoms. 

The Soviet workers determined the constitution of roemrefine (=reframine methohydroxide) (56a) (286,574), and Dyke and Ellis confirmed the position of the phenolic group on the aromatic ring in amurensine (56b) by a synthesis (575, 576). The alkaloids thalisopavine (417) and O-methylthalisopavine (248), isolated from Thalictrum dasy-carpum (Ranunculaceae), have the same absolute configuration as the other known isopavine alkaloids obtained from Papaveraceae plants. 

The isopavines reframine (34) and reframidine (35) have been synthesized by established routes. The details of the conventional synthesis of the pa vine bisnorargemonine and related isomers have been given, together with the appro-... 

From 7 . refracta, Konovalova et al. (112) isolated (-)-roemerine (115) as the major alkaloid and a smaller quantity of L-(-)-ephedrine and o-(+)-pseudoephe-drine. Yunusov et al. (113) isolated, in addition to roemerine, a low yield of anonaine (114), liiiodenine (157), and remrefine (66). On the contrary, ano-naine, liriodenine, and ephedrine could not be proved by Slavik et al. (114), who found reframine (65) and roemerine as the major alkaloids. 

Re amidine, reframine, teframoline, retnrefine (= reframine methohydroxide) Proaporphines... 

The methylenedioxy substituted isopavine amurensine was prepared by a parallel method, as were the related bases reframine and reframoline. In the latter study, undertaken to confirm the structure of reframoline, the two positional isomers with respect to the hydroxyl and methoxyl groups, namely, 5 and 6, were prepared synthetically, but could not be distinguished by spectral means. They were, however, easily characterized by way of the UV spectra of their respective methine bases, 7 and 8. The 3-hydroxy methine base exhibited a large bathochromic shift upon the addition of base, while little alteration of the spectrum of the 2-hydroxy isomer occurred in base ... 

Umezawa and co-workers have succeeded in improving the yields in the transformation of benzylisoquinolines to isopavines. Lead tetraacetate oxidation of 6-hydroxy substituted tetrahydrobenzylisoquinolines generates C-4 acetoxylated products which in acid cyclize to isopavines in over 90% yield. The syntheses of reframine and 0-methylthalisopavine are examples of this method. By contrast, the yields in the acid-catalyzed cyclization of 4,7-dihydroxy-tetrahydrobenzylisoquinolines to isopavines rarely exceed 30-35% ... 

---