Distribution and Biosynthesis of Iridoid Glucosides in the Loasaceae Family

In order to make a more precise inventory of iridoid glucosides from Loasaceae family 13 species belonging to 7 genera (Eucnide bartonioides, E. grandiflora, Gronovia scandens, Fuertesia domingensis, Loasa parviflora, L. tricolor, L. urens, L. speciosa, Klaphrotia mentzeloides, Cajophora cernua, C. lateritia, Blumenbachia hieronymi) were investigated. Six new compounds were isolated and fully characterized. From E. bartonioides, a novel iridoid named 5-hydroxyloganin, was isolated and characterized by NMR. While a novel pair of secoiridoids, 6alpha/beta-hydroxysweroside, were obtained from Gronovia scandens. A new oleoside-type secoiridoid, named 10-hydroxyoleoside 7-methyl ester was isolated from Cajophora cernua. Finally, two new secoiridoids were found in C. lateritia, namely 10-acetoxyoleoside 7-methyl ester and 10-acetoxyoleoside 11-methyl ester. The phytochemical work for the rest of the species investigated revealed only known compounds. - In order to elucidate the biosynthesis of secoiridoids found in the Loasaceae family, the synthesis of four possible 2H labelled precursors ([6,7,8,10-2H4]-deoxyloganic acid, [6,10-2H2]-ketologanin, [6,10-2H2]-ketologanic acid, and [6,10-2H2]-7-epi-loganic acid)were performed. additionally, one 13C labelled precursor (13C-stanside) was synthesized. - The introductory administrations of 2H labelled precursors to E. bartonioides, E. grandiflora and C. lateritia demonstrated that deoxyloganic acid is significantly incorporated into several sweroside-morroniside type secoiridoids present in these species. - Deoxyloganic acid and loganin were shown to be incorporated into morroniside in E. bartonioides and E. grandiflora. Ketologanin was also incorporated into morroniside in E. bartonioides. The incorporations obtained in Eucnide supports a biosynthetic route from deoxyloganic acid through loganin and ketologanin, which is suggested to be the precursor that undergoes ring cleavage to morroniside.- In C. lateritia loganin also proved to be a precursor of 10-acetoxyoleoside 11-methyl ester whereas 7-epi-loganic acid was not incorporated at all. The incorporations obtained in C. lateritia support a different biosynthetic route for oleoside-type iridoids in the Loasaceae family in comparison with Oleaceae family. - Finally, the implications of the biosynthetic and the phytochemical studies on the taxonomic placement and phylogenetic relationships of Loasacae are discussed. It is difficult to establish phylogenetic relationships within the Loasacae family using the iridoid distribution pattern known until now. The iridoids and secoiridoids present derive from the biosynthetic route I, which is shared by Cornales, Gentianales and Loasales. The presence of 10-decarboxylated iridoids is common for the genus Mentzelia (Loasaceae) and the family Hydrangeaceae (Cornales). And finally, the presence of oleoside-type secoiridoids in Loasaceae, which is shared by the family Oleaceae (Gentianales), confirm a common ancestry for Cornales, Gentianales and Loasales. However, the presence of the oleoside-type iridoids in Loasaceae and the differences of the biosynthetic pathways between Oleaceae and Loasaceae justify the placement of Loasaceae in its own order near to Cornales and Gentianales as suggested by Dahlgren.