(–)-(1R,2R,7S,8aR)-1,2,7-Trihydroxyindolizidine [(–)-7S-OH-Lentiginosine]: Synthesis and Proapoptotic Activity

An improved approach for the preparation of enantiopure 3,4- bis-tert-butoxypyrroline N-oxides is presented. Etherification of 1-benzylpyrrolidine-3,4-diol with tBuOAc/HClO4 and subsequent N-debenzylation and pyrrolidine oxidation with oxone affords the cyclic nitrone reliably and in superior yield. The enantiomer derived from d-tartaric acid was exploited in a modified synthesis of ()-7S-OH-lentiginosine. The activity of this trihydroxy indolizidine in inducing the apoptosis of tumour cell lines of lymphoid and epithelial origin is examined.