RAKOTONDRAMASY

Rice is a monocotyledonous plant in the Poaceae family. The cultivation of this cereal is prevalent in Madagascar. It is the staple food of the Malagasy people. This study concerns the determination of the lethal dose 50 of the X243 variety rice root by administering three different doses: 100 mg/kg, 500 mg/kg, and 2048 mg/kg of the body weight of a Swiss-type albino mouse. The doses administered gave two values of LD50. The logarithmic value is 1258,93 mg/kg body weight, and the linear value is 1495,24 mg/kg. These values are very close. Consequently, the roots of the X243 variety rice are toxic. Moreover, phytochemical screening shows the presence of alkaloids, tannins, polyphenols, and cyanogenic compounds. There’s no doubt that cyanogenetic compounds are extremely poisonous and responsible for poisoning. Our results confirm the presence of poison in the rice roots already known to the population.

Five new unsaturated iridolactones 3–7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.

Treatment of aucubin (1) with tert-butyldimethylsilyl chloride under alkaline conditions permitted regioselective silylation of either the primary hydroxyl groups at C-9 and C-6' or both primary hydroxyl groups and the secondary allylic hydroxyl group at C-6. Acetylation with acetic anhydride, followed by selective removal of the silyl groups and Mitsunobu reaction involving phthalimide as nitrogen donor, gave a stereospecific entry to aminoside antibiotic analogues: 10,6'-diamino-10,6'-dideoxyaucubin (16) and (6R)-6,10,6'-triamino-6,10,6'-trideoxyaucubin (17).

The novel iridoid glycoside 2 was prepared in six steps (15% overall yield) from natural aucubin (1) and fully characterized. Compound 2, which comprises the same conjugated cyclopentenone pharmacophore as known antitumor oxylipins and prostaglandins, displayed significant antiproliferative in vitro activity towards leukemia L1210 cells. The Michael addition of nucleophilic thiols to compound 2 occurred on a different position compared to classical Δ7-prostaglandin A1 methyl ester. The resulting adducts 7a and 7b were fully characterized, and their MS fragmentation patterns were elucidated.