Development of a flexible approach to Nuphar alkaloids via two enantiospecific piperidine-forming reactions.
In this paper we describe the stereoselective synthesis of functionalized lactam 7 via two enantiospecific piperidine-forming techniques and its employment in a general synthetic approach to Nuphar alkaloids. Specifically, the formation of piperidine 18 by formal [3 + 3] cycloaddition and stepwise annelation processes is described; the latter technique was found to be significantly more efficient than the Pd-catalyzed TMM addition process. Finally, exploitation of the exocyclic alkene installed in the piperidine-forming reaction in the transformation of 18 to (-)-deoxynupharidine ((-)-2), (-)-castoramine ((-)-3), and (-)-nupharolutine ((-)-4) via intermediate lactam 7 is delineated.
Goodenough
Katharine M
KM
Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Moran
Wesley J
WJ
Raubo
Piotr
P
Harrity
Joseph P A
JP
D000470:Alkaloids / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007769:Lactams / Q000737:chemistry; D015394:Molecular Structure; D031654:Nuphar / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011807:Quinolizines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000470:Alkaloids; D007769:Lactams; D010880:Piperidines; D011807:Quinolizines; C010908:deoxynupharidine; D010165:Palladium; C032727:piperidine