Four new α-pyrones, hypotiens A-D (1-4), were isolated from a fungal endophyte, Hypoxylon investiens J2, harbored in the medicinal plant Blumea balsamifera . Their structures were determined through detailed HRMS and NMR spectroscopic data. Compounds 1-4 are new α-pyrone derivatives containing an unusual dimethyl substitution in the highly unsaturated side chain. Their plausible biosynthetic pathway was discussed. Biological assay indicated that compounds 1-4 showed no antimicrobial, quorum sensing inhibitory, and cytotoxic activities. The specific side chain in α-pyrone derivatives 1-4 might be responsible for the weak pharmacological activities.