Enantiospecific synthesis of (-)-slaframine and related hydroxylated indolizidines. Utilization of a nucleophilic alaninol synthon derived from serine

A general methodology for the synthesis of indolizidine alkaloids delta-con iceine (12), 1-hydroxyindolizidine (20), desacetoxy slaframine (24), slafra mine (34), and an analogue (37) has been developed. This convergent approac h utilizes the available chirality in proline and serine and is conceptuall y different from other approaches. A highly stereoselective coupling of the prolinals with a nucleophilic alaninol synthon provides the precursors for the key cyclization. A novel thermolytic annulation of an oxazolidinone is the key step in the formation of the six-membered piperidine ring. Further elaboration provides the target natural products 24, 34, and 37 in good ov erall yields.