Part~I. Total synthesis of epibatidine homologs. Part~II. Nitrogen insertion reactions of bridged bicyclic ketones: A: Substitutent effects on the regiochemistry of the Schmidt reaction of 7-substituted bicyclo(2.2.2)heptan-2-ones. B: Attempted regioselective nitrogen insertion using chiral alpha-methylbenzylnitrones.

摘要

art I. Epibatidine, an alkaloid found in the skin of Epipedobates tricolor frog, is one of the most potent analgesics described to date. It has been found to be 200-500 times as potent as morphine, but it has a very narrow margin of safety. Further work on epibatidine related structures may provide useful compounds for study of nicotinic receptors in the brain. We have synthesized epibatidine homologs: (;Part II. A: The Schmidt reaction of bicyclo (2.2.1) heptan-2-one affords methylene migrated (NM) lactam in addition to cleavage products. The Schmidt reactions of 7-anti and syn substituted bicyclo (2.2.1) heptan-2-ones give both methylene migration (NM) and bridgehead migration (NBH) products. The results are consistent with rearrangements occurring via iminodiazonium ions but not tetrahedral protonated azidohydrins.;Part II. B: Attempts to control the regiochemistry of nitrogen insertion in the Barton modification of the Beckmann reaction using