Pyrrolizidine alkaloids structural determinants

Monocrotaline (170) has been the subject of extensive metabolic study with mammalian and microbiological systems. Pyrrolizidine alkaloids such as monocrotaline require metabolic activation to the corresponding pyrrole derivatives or dehydro alkaloids before they are capable of forming covalent bonds with critical macromolecules within the cell. The X-ray structure of dehydromonocrotaline has recently been determined (226), and the ability of dihydroretronicine derived from monocrotaline to react with deoxyguanosine has been demonstrated in vitro (225). 

The crystal structures of pyrrolizidine alkaloids that have been determined may be divided into structural groups on the basis of the necine they contain. Alkaloids with retronecine (127) as base are fulvine and axillarine, which both have an 11-membered macrocyclic diester ring, and jacobine and swazine, which contain 12-membered diester rings. Heliotrine is a C-9 monoester of heliotridine (109). Retusamine, clivorine, and senkirkine, all include otonecine (125) as the base portion. The alkaloids... 

A number of closely related naturally occurring pyrrolizidine cyclic ethers have been identified.74 Four of these, loline (=festucine75) (119), norloline (120), lolinine (121), and decorticasine (122), have had their structures and relative configurations established by chemical methods. In addition, the relative stereochemistry of loline has been defined by an X-ray crystal structure determination of its dihydrochloride.76 The absolute configurations for all these alkaloid bases have now been established by the X-ray technique of anomalous dispersion using the same dihydrochloride of loline (119).7 7... 

Gramain J-C, Remuson R, Vallee-Goyet D, Guilhem J, Lavaud C (1991) Total synthesis and determination of structure of the pyrrolizidine alkaloid curassanecine. J Nat Prod 54 1062-1067... 

A very large range of pyrrolizidine alkaloids can theoretically be obtained by combining the known necines and the esterifying acids (= necic acids). So far, more than 500 alkaloids have been found and their structures determined. With the exception of the approximately 35 otonecine alkaloids that cannot form N-oxides, if the N-oxides of these alkaloids are taken into consideration, more than 900 structures are known. 

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. 

---