Total Synthesis of Neuroprotective Agents, (+)-Lycibarbarine A and (-)-Lycibarbarine B

We describe the convergent total syntheses of lycibarbarines A and B which are potent neuroprotective agents recently isolated from the fruits of Lycium barbarum. The synthesis highlights the construction of a unique spiro oxazine heterocyclic motif imbedded in these natural products. The synthesis is accomplished from the commercially available 8-hydroxyquinaline and 2-deoxy-d-ribose as key starting materials. The synthesis features a Reimer-Tiemann reaction, selective amine alkylation with a keto tosylate derivative, and spiroketalization to form an oxazine core.