The isolation and structure elucidation of flutimide (1), an inhibitor of flu transcription endonuclease from Delitschia confertaspora, a new species, is reported. The novel natural product is characterized by N-hydroxyimide and exocyclic enamine functionalities. Influenza, an acute contagious respiratory disease is caused by influenza viruses A and B. The distinguishing characteristics of influenza are the mortality that can result from pulmonary infection which periodically causes epidemics. Influenza virus is a negative strand RNA virus with a segmented genome. Its mRNA synthesis is catalyzed by a virally-encoded transcription complex. This virus uniquely utilizes capped and methylated (cap 1) primers for its mRNA synthesis. Endonuclease, a unique enzyme that cleaves the capped cellular transcripts for further RNA elongation is critical for viral replication. Thus inhibition of this enzyme could be potentially useful as a therapeutic target towards development of an anti-influenza drug. The novel natural product flutimide (1) was isolated from Delitschia confertaspora, a new species, collected from dung of a dassie in Namibia, using a Flu transcription biological screen. It selectively inhibits endonuclease and shows antiviral activity in cell culture. The titer of flutimide in the fermentation broth was very low and very difficult to improve. Only ~1 mg of material was initially available for structure determination which did not allow a clear distinction between 1 and the isomeric hydroxamic acid structure 2 to be made based on NMR and MS evidence alone. This was resolved in favor of 1 by synthetic and degradative studies when more of 1 became available. We report here on the isolation and structural studies of flutimide, corroboration of which was obtained by an unambiguous synthesis from L-leucine.