Proaporphines

The following secodimeric alkaloids have been isolated from natural sources (+)-hernandaline (197), from Hernandia ovigera L. (158), (—)-natalinine (198) (759), and (+)-coyhaiquine (199) (160), the two latter from Berberis empetrifolia Lam. with the yields 0.00005 and 0.00008%, respectively. Appropriate aporphine-benzylisoquinoline or proaporphine-benzylisoqui-noline dimers are probably precursors of these seco alkaloids, although... 

C. Aporphine, oxa-aporphine, and proaporphine alkaloids (including dioxo-... 

Pakistanamine (46) was first characterized in 1973, and the absolute configuration was determined at C-6a, but not at C-13. In 1982, extensive proton NMR decoupling and NOE experiments (Section VI,A,2) were reported that made possible a complete stereochemical assignment of pakistanamine and, by extension, of five other (see Section II,C,6) benzylisoquinoline-proaporphine dimers. The protons of 46 were first assigned by spin decoupling of particular interest... 

Chitraline is obtained from B. baluchistanica under neutral conditions, so it is an actual alkaloid and not an artifact from acid-catalyzed dienone-phenol rearrangement of a proaporphine-benzylisoquinoline dimer (61). Chitraline has also been isolated from B. zebiliana Schneider (62), and B. calliobotrys (62). A possible biosynthetic scheme relating chitraline with co-occurring alkaloids has been proposed (62, see Section VII,C). 

Coyhaiquine (107), C26H27N05, from Berberis empetrifolia Lam. (Ber-beridaceae), although not formally a bis alkaloid, appears to be derived by in vivo degradation of a proaporphine-benzylisoquinoline. NMR spin decoupling experiments assigned the chemical shifts of the 6a, 7a, and 7(3 hydrogens. NOE experiments then showed a 3% enhancement of the 7a-H on irradiation of the 8-H, establishing the indicated syn stereochemistry (64). 

Epivaldivianine (476), C37H40N2O6, amorphous, from Berberis valdiviana Phil., has [a] 5 +69.4° (c 0.1, MeOH). Structure proof consisted of NMR correlations and rearrangement of the alkaloid in acid to the known (—)-kalashine (177). Epivaldivianine is the third epi proaporphine-benzylisoquinoline dimer (the first two being 108 and 475) (557). 

M. Shamma and H. Guinaudeau, Tetrahedron 40, 479S (1984). Biosynthesis of aporphinoid alkaloids. In addition to monomeric alkaloids, discusses proaporphine- and aporphine-benzyliso-quinoline dimers, dimeric oxidized aporphines, and types derived by catabolism of benzyliso-quinoline-derived dimers. 

Pronuciferine (1) has been synthesized by photocyclization of the brominated phenol (2).9a The light-induced rearrangement of proaporphines yields aporphines that are substituted at C-9 or at both C-8 and C-9.5 This topic is further discussed below, under the sections on aporphines and aporphine dimers. The known alkaloid N-methylcrotsparine has been found in Pachygone ovata.9b... 

Several groups have examined the 13C spectra of the aporphine alkaloids (6, 7, 38-40) examples are found in Fig. 10. The chemical shift assignments (Table X) for the aliphatic carbon atoms of rings B and C were made by comparison to laudanosine (28) (6) and to the reduced proaporphines (41). In the case of caaverine (49) a comparison with (+)-lirmidine (50) revealed the P deshielding effect of the TV-methyl group on C-5 and C-6a and the shielding of C-7 by a y effect. 

The 13C chemical shifts of several reduced (61-64) and nonreduced (65, 66) proaporphine alkaloids (Fig. 11 and Table XI) have been reported by Ricca and Casagrande (41). The authors studied several pairs of diastereo-mers and found the 13C chemical shifts to be sensitive to the relative stereochemistry in these compounds. 

In the nonreduced proaporphines, (— )-glaziovine (65) and ( —)-pronuci-ferine (66), the additional double bond in ring D results in a shielding of the carbonyl carbon. Similar observations have been made in other cross-conjugated system (8, 42). 

Morphinandienones have also been synthesized by the oxidation of mono-phenolic benzylisoquinolines with vanadium oxyfluoride in trifluoroacetic acid, other products of the reaction being proaporphines, and similar oxidations have been accomplished with phenethylisoquinolines.183 The same reagent will oxidize the lactam (150) to the dienone (151), which is an analogue of dehydrometatheb-ainone, and the same cyclization may be effected by electrochemical oxidation.184... 

N-Methyl-litsericine (1), a new proaporphine alkaloid, has been isolated from Neolitsea aurata.5... 

The phenolic proaporphine alcohols produced by reduction of (2) and of 8,9-dihydroglaziovine with sodium borohydride have shown anxiolytic and antidepressant activity in rabbits.8... 

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