Total synthesis of (+/-)-quinolizidine 217A

Several 1,4-disubstituted quinolizidines have been isolated in minute quant ities from the skin of certain poisonous frogs and toads. The structures of these alkaloids have been proposed mainly on the basis of MS and IR spectr oscopic data. We report the first total synthesis of a naturally occurring alkaloid of this type, quinolizidine 217A. After examination of several azi de-based routes, the cyclization of an azide onto an ester-bearing alkene p rovided a 3,4,5,6-tetrahydropyridine that was reduced in a stereoselective fashion to produce a cis-2,6-disubstituted piperidine (25 --> 31 --> 32). T ransformation of 32 into quinolizidine 217A (2) and its C(1) epimer (41) we re accomplished in a straightforward fashion. Synthetic quinolizidine 217A was found to be identical to the natural alkaloid, confirming its stereostr ucture. Compound 41 has the same stereostructure as that proposed for the a lkaloid quinolizidine 207I, a compound whose configuration was recently rev ised as a result of synthetic studies by Momose et al., who synthesized a 1 ,4-disubstituted quinolizidine with the configuration previously proposed f or quinolizidine 207I and found the synthetic material to be epimeric with the natural material. Compound 41 should provide a useful point of comparis on for future studies on the stereostructure of natural or synthetic quinol izidine 207I.