The enantiopure (2S,3S,3aS,5S)-1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-2,3,5-triol (2,3,5-trihydroxybenzo[e]indolizidine) framework has been synthesized by a straightforward strategy consisting of 1,3-dipolar cycloaddition of a [a] 4879 pyrroline N-oxide to 2-bromostyrene followed by isoxazolidine N-O bond reduction and cyclization by copper-catalyzed nucleophilic aromatic substitution of the intermediate pyrrolidine.Scheme 3. Reductive ring opening of the major adducts 9a-11a.www.eurjoc.org

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.

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