Senecio alkaloids structure

Sencor — see l,2,4-Triazin-5-one, 4-amino-6-t-butyl-3-methylthio-Senecio alkaloids structure, 7, 658 Senepoxide, 7, 192 Senkirkine conformation, 7, 703 structure, 7, 658 Sensitizing dyes... 

Some Senecio alkaloids have opened pyrrolizidine ring systems which show transannular interactions and are closely related in structure to the compounds discussed above. The alkaloid senkirkine is a cyclic ester of (37) (74JA6165) and its X-ray structure shows a rather short transannular contact of 2.23 A. 

The Senecio alkaloids discussed above are esters of mono-, di-, and trihydroxy-1-methylpyrrolizidines, and a few of these necine bases or their derivatives have been found free in the plant. The pyrrolizidine structure has more recently been found in a number of other alkaloids. 

Of all the Senecio alkaloids, the structure of monocrotaline is known with most certainty as a result of the work of Adams and his co-workers over a period of five years or more. The alkaloid monocrotaline (I) is the ester of retronecine vith monocrotalic acid. The structure of the necine portion has been proved conclusively, while the structure of the necic acid portion is considered the most likely of three possible configurations. The position of attachment of the two portions is known with certainty. The... 

These illustrations may be regarded as typical experimental procedures for the extraction, hydrolysis, and hydrogenolysis of a Senecio alkaloid. In order to assign a structure to a particular Senecio alkaloid, it is first necessary to prove the structure of the portions obtained on hydrolysis and hydrogenolysis of the alkaloid. Accordingly, the structure of the necines and necic acids will be considered before that of the parent alkaloid, which is necessarily represented by their combination. 

The pyrrolizidine ring structure (V) was not known prior to the discovery of its presence in the Senecio alkaloids. 

The comparison between values of unsaturated and saturated amines may be of aid in placing the unsaturation. Thus the senecio alkaloids 102, 104, and loio were correctly assumed to be aUylamines because their p/T values are lower than those of the saturated alkaloids 103,105, and 107 (Table 17). The vinylamine structure was discarded in these, as basicities higher than those of the corresponding saturated compounds would be expected The opposite should be true in the case of neostrychnine (101), a vinylamine unable to react according to equation (75), and therefore less basic than strychnine (108), an aUyl-amine in which the — / effect of the unsaturation on the amino group is weakened by distance (Table 17) °. ... 

This alkaloid, C20H31ON (mp 185°), from Thelepogon elegans Roth (Gramineae) (232) forms a methiodide (mp 255°) which was used for the determination of its absolute structure (LXXXVII) by X-ray analysis (233). Structurally, the pyrrolizidine portion closely resembles the basic fragment of the Senecio alkaloids and the carbon skeleton finds some analogy with the terpenoid, manool. 

Coucourakis, E. D., and C. G. Gordon-Gray The Senecio Alkaloids. Suggested Structures for Isoline and Bisline, Two New Alkaloids from Senecio othonniformis Fourcade. J. Chem. Soc. (C) 1970, 2312. 

Alkaloids arc not uncommon in the family but many arc of unknown structure. They include amides, found in several genera, which have been considered alkaloids in the broadest sense. Perhaps most familiar of all are the alkaloids of Senecio and relatives, which are of importance as slock poisons. 

The known alkaloids senecionine, senkirkine, and retrorsine have been isolated from Senecio vernalis Wald, et Kit. by Roder et al.26 A new alkaloid, named senecivernine (59), was also present. The mass spectrum of (59) showed a molecular ion at m/z 335, and fragment ions at m/z 291, 248, and 220, characteristic for a macrocyclic diester of retronecine, arising from cleavage of the allylic ester.17 Basic hydrolysis of senecivernine gave a new necic acid which had spectroscopic data in accord with the proposed structure. Retronecine was not isolated. The necic acid from senecivernine is a Ci0 acid of an unusual structural type (cf. Vol. 8, p. 55). 

Bulgarsenine (61) has also been isolated from Senecio doronicum L. together with a new alkaloid, doronenine (62).28 The structure and absolute configuration of doronenine were established by X-ray structure analysis.29 The structure (63) of the saturated y-lactone (ds-nemorensic acid) that was obtained on alkaline hydrolysis of doronenine was also determined by X-ray crystallography.30... 

Pyrrolizidine alkaloids in the plant Senecio vernalis have been implicated in the poisoning of cattle.13 The toxic agents in this plant include three closely related alkaloids — senecionine, senkirkin, and seneciphyllin. The structural formula of senecionine is shown in Figure 19.2. 

The presence of pyrrolizidine alkaloids in arctiid moths that had been reared on Senecio and Crotalaria species has been established by Rothschild et al.4S These alkaloids are stored in the moths, and serve as a deterrent to vertebrate predators and as precursors for insect sex pheromones. A pyrrolizidine alkaloid metabolite from the Cinnabar moth (Tyria jacobaea L.), named callimorphine, has been shown to have the structure (49) on the basis of mass-spectral and degradative evidence.46 The structure (49) was confirmed by synthesis of callimorphine and a diastereo-isomer by treatment of 9-chlororetronecine with the sodium salt of ( )-2-acetoxy-2-methylbutanoic acid. 

Figure 9.2. Metabolism of pyrrolizidine alkaloids (PAs) in Senecio vernalis. The substrates for alkaloid biosynthesis, putrescine and spermidine, are derived from primary metabolism. Homospermidine, synthesized by homospermidine synthase (HSS), is the first pathway specific intermediate. It is exclusively incorporated into the necine base moiety of senecionine A-oxide, the backbone structure of all PAs found in this Senecio species. During allocation from the roots as site of synthesis to the shoots, it is chemically modified to provide the species specific PA-pattem.

Fig. 13.14 The reversed phase HPLC-ESI-MS base ion (mjz 200-500) chromatograms for, and structures of some pyrrolizidine alkaloids identified in extracts of Senecio jacobaea and S. ovatus. The peak labels are referred to in the text.

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