ANALOGS AND BIOISOSTERES OF PYRROLIZIDINE ALKALOIDS

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Recently we have developed enantiospecific reactions for the synthesis of antipode (mirror image form) of substituted 3- lactams. Appropriately substitute-beta-lactams can be converted in stereospecific fashion to optically pure alkaloids of various types. We propose to further develop these synthetic methods and synthesize a variety of pyrrolizidine alkaloids (naturally occurring as well as those not known in nature) in both antipodal forms. Also to be synthesized are some related indolizidine and quinolizidine derviations as well as pyrrolizidine analogs in which one of the ring carbons has been replaced by a hetero atom. Several pyrrolizidine alkaloids are known to be carcinogens. Some of these substances enter our food chain through contaminated grains or herbal medicines and teas. Livestocks are infected through the consumption of forage plants containing pyrrolizidine alkaloids. Cow's milk and honey are sometimes carriers of these alkaloids. Semisynthetic pyrrolizidine bases have been found to possess a wide variety of biological activity. Chiral pyrrolizidine bases and their aza-, oxa- or this-analogs and other alkaloids prepared by us would be tested for a range of biological activity by a pharmaceutical company. Some of the chiral syntheses developed are expected to be more enantioselective or simpler than the alternative syntheses in the literature.