Discovery and Biomimetic Semisynthesis of Spirophyllines A–D from Uncaria rhynchophylla

Spirophyllines A–D (1–4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3′-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1–8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 μM).