Crotalaria medicaginea Associated with Horse Deaths in Northern Australia: New Pyrrolizidine Alkaloids

Crotalaria medicaginea has been implicated in horse poisoning in grazing regions of central-west Queensland, which resulted in the deaths of more than 35 horses from hepatotoxicosis in 2010. Liver pathology was suggestive of pyrrolizidine alkaloidosis, and we report here the isolation of two previously uncharacterized pyrrolizidine alkaloids from C. medicaginea plant specimens collected from pastures where the horses died. The first alkaloid was shown by mass spectometric and NMR analyses to be 1β,2β-epoxy-7β-hydroxy-1α-methoxymethyl-8α-pyrrolizidine, which, like other alkaloids previously isolated from C. medicaginea, lacks the requisite functionality for hepatotoxcity. The second alkaloid isolated in this investigation was a new macrocyclic diester of otonecine, which we have named cromedine. The 1H and 13C NMR spectra of cromedine were fully assigned by 2D NMR techniques and allowed the constitution of the macrocyclic diester to be assigned unambiguously. C. medicaginea specimens implicated in this investigation do not belong to any of the three recognized Australian varieties (C. medicaginea var. neglecta, C. medicaginea var. medicaginea, and C. medicaginea var. linearis) and appear to be a local variant or form, referred to here as C. medicaginea (chemotype cromedine).