Hypoglycemic effects of multiflorine derivatives in normal mice.

(-)-Multiflorine isolated from leguminous plants produces a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone-type conjugation on the A ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the hypoglycemic effect, several compounds bearing the quinolizidin-2-one ring system were synthesized, and their hypoglycemic effects were examined. In addition, tricyclic compounds bearing 4-pyridone were synthesized, and their hypoglycemic effects were examined. The hypoglycemic effect of a 4-pyridone-type compound was similar to that of (-)-multiflorine as measured by oral glucose tolerance testing in normal mice. No hypoglycemic effect of a 4-piperidone-type compound was observed. These results indicate that compounds possessing double bond(s) in the A ring of multiflorine may be lead compounds for a new type of diabetes drug.