Dihydroatisine

The von Braun Reaction with Dihydroatisine.—Indian researchers37 have reported a study of the von Braun reaction of dihydroatisine (29) and a mass spectral analysis of the resulting product, the N-nitrile (93). Reduction of atisinium chloride (94) with sodium borohydride gave dihydroatisine (29). The reaction of the latter with cyanogen bromide in anhydrous ether at room temperature for 24 hours gave (93) [m.pt 265 °C] in a yield of 86%. Acid hydrolysis of (93) with 10% HC1 afforded compound (95). 

Dihydroatisine, a minor alkaloid of the roots of A. heterophyllum Wall, was isolated (SO) from the strong base fraction and its structure (78) was established by comparison with the sodium borohydride reduction product of atisine or isoatisine. Recently, an X-ray analysis of dihydroatisine confirmed (30) its structure and determined the absolute configuration as 45, 55, 87 , 107 , 127 , and 155. So far dihydroatisine has not been reported in any other plant. 

Veatchine acetate (210) was hydrolyzed to veatchine (1) in methanol at room temperature without using any external base (152). This unusual hydrolysis was explained by participation of methoxide ion which was formed by opening of the oxazolidine ring by methanol. Diterpenoid alkaloid derivatives lacking the oxazolidine ring, such as dihydroatisine diacetate (211) and veatchine azomethine acetate (10), failed to give compounds 212 and 78, respectively, in methanol under these conditions. 

Atisine hydrochloride (1.2 g.) with methanol (20 ml.) saturated with sodium hydroxide at 100° for 90 hr. (sealed tube) gives, on dilution and ether-extraction, dihydroatisine (75%). 

A full report on the C n.m.r. studies of these and related compounds and a rebuttal of some of the previously published n.m.r. spectral interpretations (cf. this Report, 1978, Vol. 8, p. 238) have appeared. The rebuttal was submitted prior to the publication of the X-ray crystallographic studies. n.m.r. spectral data were reported for atisine (1), atisinone (68), isoatisine (66), isoatisinone (69), dihydroatisine (65), dihydroatisine diacetate (70), atidine (71), atidine diacetate (72), atisine azomethine (73), atisine azomethine acetate (74), atisine dihydro-azomethine (75), atisine A-methyl dihydro-azomethine (76), veatchine [(67a) and (67b)], garryine (77), dihydroveatchine (78), dihydroveatchine diacetate (79), veatchine azomethine (80), veatchine azomethine acetate (81), veatchine dihydro-azomethine (82), and veatchine X-methyl dihydro-azomethine (83). 

Gonzalez et al. have reported that three molecules of the C2o-diterpenoid alkaloid group 15,22-0-diacetyl-19-oxo-dihydroatisine, azitine, and isoazitine exerted antiparasitic activity on promastigotes and intracellular amastigotes of Leishmania infantum [57, 58],... 

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