Two hundred and thirty-seven endophytic fungi were isolated from the endemic plant Desmotes incomparabilis (Rutaceae), collected in Coiba National Park, Veraguas, Panama, by Alicia Ibañez (STRI, Panama City). Because it showed high biological activity in prescreening assays, the fungus Mycoleptodiscus sp. F0194 was chosen for additional study. In this paper we describe the isolation and structural elucidation of two novel reddish-orange alkaloids, which we have named mycoleptodiscin A (1) and mycoleptodiscin B (2).