Hypoglaucines A-D, Unusual Isoquinoline Dimers from the Roots of Cyclea hypoglauca

Hypoglaucines A-D (1-4), four unusual isoquinoline dimers, were isolated from the roots of Cyclea hypoglauca. Compound 1 features p-tolylmethanol and 4-(hydroxymethyl)phenol linkages that join two isoquinoline monomers into a 19-membered macrocyclic ring. Compounds 2-4 are bisbenzylisoquinoline derivatives containing a benzoyl unit. The structures of 1-4, including their absolute configurations, were determined by spectroscopic, computational, and single-crystal X-ray diffraction methods. Compound 1 potently inhibited the proliferation of NCI-H1975 cells with an IC50 of 1.43 ± 0.15 μM by inducing G0/G1 phase arrest.