Bioactivity-directed fractionation of the fermentation broth and mycelium of the coprophilous fungus Guanomyces polythrix led to the isolation of several phytotoxic compounds, including five new naphthopyranone derivatives (1-5). In addition, rubrofusarin B, emodin, citrinin, and 4-hydroxybenzoic acid methyl ester were obtained. The structures of the new compounds were established by spectral and chiroptical methods. The isolates caused significant inhibition of radicle growth of two weed seedlings (Amaranthus hypochondriacus and Echinochloa crusgalli) and interacted with both spinach and bovine brain calmodulins.