Cryptaustoline iodide

Ewing et al. (2) noted that C. bowiei, a small shrub in New South Wales and southern Queensland and a tree growing to about 10 m (30 feet) in northern Queensland, afforded alkaloids which were different but structurally closely related. Methods of isolation were essentially the same, and the alkaloids were obtained as sparingly soluble iodide salts after addition of potassium iodide. (—)-Cryptaustoline iodide (C20H24NO4I) was obtained from extracts of the bark of larger northern trees, and (-)-cryptowoline iodide (C,gH2oN04l) was found to be present in the smaller southern shrubs. 

Major efforts to determine the structures of the optically active alkaloids were made with cryptaustoline iodide, and preliminary examination showed that the molecular formula could be expressed as CjgHjj(OH)(OCH3)3(NCH3)" I . Products obtained after Hofmann degradation and ozonolysis were identical with compounds obtained earlier by Robinson and Schopf from racemic 14, and the structure as one of the optical isomers of O-methylcryptaustoline iodide was established. 

Following the successful demonstration of an enamine photocyclization, Ninomiya synthesized ( )-cryptaustoline iodide from 44b. Irradiation of isopropyl ether 44b gave a mixture of dibenzopyrrocolines 45b and 45c in 12 and 11% yield, respectively. The isopropyl ether group in 45c was selectively hydrolyzed by hydrobromic acid, and the resulting phenolic compound was converted to cryptaustoline iodide with methyl iodide. An attempt to photocyclize an O-benzyl ether analog of 44b was less satisfactory. 

Cryptaustoline (1) and (-)-cryptowoline (2) were obtained as iodides from the Australian plant Cryptocarya bowiei (Hook) Druce, and their structures... 

The structure of cryptowoline iodide (2) was determined by a similar set of reactions. Both O-methyl and 0-ethyl ethers were subjected to exhaustive meth-ylation, elimination, reduction, and ozonolysis. The key compounds obtained from the ethyl ether were 26 and 6-aminopiperonal. The amine fragment showed the methylenedioxy group to be at the 9,10 position in cryptowoline, and the fact that the same aldehyde 26 was obtained from 0-ethylcryptowoline iodide fixed the position of the free OH as in cryptaustoline to C-2. 

Synthesis of (-)-O-methylcryptaustoline iodide (14) from (S)-(-)-laudanoso-line by chemical and later by enzymatic means (vide infra) established the (5) configuration at C-12a in cryptaustoline (7). The stereochemistry of the N-methyl group in 1 has not been determined. 

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