(+/-)-Spiroganoapplanin A, a complex polycyclic meroterpenoid dimer from Ganoderma applanatum displaying potential against Alzheimer's disease

(+/-)-Spiroganoapplanin A (1) representing a new subtype of the Ganoderma meroterpenoid dimer with a 6/5/5/6/5/6 hexacyclic system was isolated from Ganoderma applanatum. Using spectroscopic, X ray crystallographic and electronic circular dichroism analyses, the structure of the racemic natural product was determined, and its unusual NMR behavior was investigated by variable-temperature NMR experiments. The possible biogenetic pathway for 1 was proposed. Cellular assays showed that (+/-)-1, (+)-1, and (-)-1 all reduce A beta 42 production and inhibit tau phosphorylation through BACE1, CDK5, and GSK3 beta-mediated pathways, suggesting their potential against Alzheimer's disease.