Hetisine alkaloids structures

Vakognavine is the first example of an N, C-19-seco-diterpenoid alkaloid reported and an interesting alkaloid for biogenetic speculation. The authors (116) suggested that the C-19 aldehyde may be a plausible alternate to the pseudokobusine structure as an intermediate in the biosynthesis of the modified atisine-type skeletons such as hetisine. The C-19 hydroxyl of vakognavine hydriodide (119) is reminiscent of the oxazolidine oxygen of isoatisine. 

Hetisine (125) was isolated as a minor alkaloid from the roots of A. heterophyllum Wall (80) in 1942 by Jacobs and Craig (118, 119). Later it was also isolated from D. cardinale Hook (120). Several papers were published (121, 122) regarding the chemistry and structure elucidation of hetisine, but the structure of hetisine (125) was eventually established by an X-ray diffraction study (123, 124). Earlier work on the chemistry of hetisine has been reviewed in Volume XII of this treatise (6). 

Alkaloids of Aconitum heterophyllum Wall.—The nature of acid-catalysed rearrangement of hetisine (61), an alkaloid isolated from A. heterophyllum and Delphinium cardinale, eluded researchers for a number of years. A compound (m.pt 278—279.5 °C) with the same molecular formula as hetisine, i.e. C20H27NO3, was isolated from A. heterophyllum. This same compound was formed by treatment of hetisine with 5% sulphuric acid.24 Wiesner and co-workers2S observed an acid-catalysed rearrangement in the formation of a methiodide of hetisine. They proposed structure (62) for this rearrangement product. 

Another well-known rearrangement, that of hetisine (43) by acid catalysis, has been re-investigated in a similar fashion. In fact two products are formed, both adamantane-1ike in structure, in ratio 19 1. Their structures, settled by nmr-spectral and X-ray analysis, are (44) and (45) respectively. The former was isolated as an alkaloid of Aaonitum hetevophyl-Iwn earlier. A pathway for the rearrangement has been sugqested (Pelletier et al., Chem. Comm., 1981, 327 Hetero-cycles, 1983, 20, 413). 

Heteratisine.—A detailed report on the chemical elucidation of the structure and stereochemistry of heteratisine (19) has appeared. This lactone diterpenoid alkaloid has been isolated along with its monobenzoyl ester from the roots of Aconitum heterophyllum Wall. Heteratisine has not been detected in any other plant. An earlier 2f-ray crystallographic analysis of the hydrobromide monohydrate of heteratisine indicated the identical structure. Heteratisine thus bears a closer structural relationship to the highly toxic and polyoxygenated alkaloids of the lycoctonine-aconitine type than to its companion bases atisine, atidine, and hetisine. 

Several diterpene alkaloids have been shown to possess structures and stereochemistries which are closely related to the hetisine structure (128), Vakognavine (129) and hypognavinol (130),which are both isolated from Aconitum plants, and spiradine A (131), " isolated from the shrub... 

This type is one of the most complex groups derived from the atisine skeleton having a heptacyclic system with an additional N-C-6 bond. A total of eight hetisine-type C2o-diterpenoid alkaloids (47-54) were isolated in the period of 2009 to Feb. 2012 [16, 41, 44 46]. Besides the complexity of the skeleton, acetyl, benzoyl, tertiary methyl, hydroxyl, O-formyl groups as well as an exocyclic double bond and a ketone make this skeleton a unique structure. 

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