Cularine methiodide

Similarities to the aporphine group extend to the occurrence of secocularine (99, R=Me) and secocularidine (99, R=H) in c. claviculata and S. crassifoHa the latter can be methylated to the former, which is identical with the product of Hofmann degradation of cularine methiodide (Boente et al.. Tetrahedron Letters, 1984, 889, 1829 Campello et al, too cit. ). 

Secocularine (28), isolated as an amorphous substance (crystallized as perchlorate) shows a characteristic UV spectrum (220, 235, 296, and 320 nm). The substitution pattern has been established from the H-NMR spectrum, which shows two singlets (6.68 and 6.92 ppm) and an AB quartet with a normal ortho coupling constant (8.3 Hz) (25). Confirmation of the structure has been obtained by synthesis. Hofmann degradation of cularine methiodide (49) with refluxing sodium hydroxide solution produces material of unknown structure (52). The same reaction, when carried out with sodium ethoxide, gives an 83% yield of a mixture of compounds 50 and 28 (25). 

Shimanouchi H, Sasada Y, Honda T, Kametani T (1973) Crystal and molecular structure and absolute stereochemistry of cularine methiodide. J Chem Soc Perkin 11 1226-1230 Shono T, Miyamoto T, Mizukami M, Hamaguchi H (1981) Electrojreductive synthesis of 1-(bromobenzyl)-isoquinoline derivatives and its application to cularine synthesis. Tetrahedron... 

Secocularine (228) and secocularidine (229) were synthesized by Hofmann degradation of the corresponding cularine and cularidine methiodides, respectively (181). Both secocularidine (229) and norsecocularine (230) were transformed to secocularine (228) by O- and N-methylation, respectively (181,182). Total synthesis of noyaine (231) was achieved by Ullmann condensation of 8-hydroxy-7-methoxy-2-methyltetrahydroisoquinoIine (232) with 6-bromoveratric acid methyl ester followed by oxidation of the intermediate 233 (183) (Scheme 35). 

Though there seemed to be no reasonable doubt about the structure of cularine it is nevertheless reassuring that syntheses of it have been reported ). A number of routes suggested by known isoquinoline syntheses failed but ultimately a maximum yield of about 8% of II (mp 133°) was obtained by treating the condensation product of the ketone (I) and aminoacetal with 75% sulfuric acid. The methiodide of II on reduction with sodium borohydride gave a satisfactory yield of d -cularine (mp 114°). 

The absolute configuration of cularine has been shown to be d = R from the optical rotatory dispersion of its hydrogenolysis product (V). The hydrochloride, methiodide, and 0-acetate of V showed complete reversal of the long w avelength Cotton effect and circular dichroism... 

---