Synthetic Studies on Echinulin and Related Natural Products. V. : Isolation, Structure and Synthesis of Echinulin-Neoechinulin Type Alkaloids isolated from Aspergillus amstelodami

Abstract

Six natural products, named E-6, E-7, E-8, E-9, E-10, and E-11, were isolated from ether and methylene chloride extracts of freeze-dried mycelium of Aspergillus amstelodami IFO-6667. E-9 and E-11 were found to be identical with neoechinulin (2) and echinulin (1), respectively, from spectroscopic and melting point data. Alkaline hydrolysis of E-7, E-8, and E-10 gave indole-3-carbaldehydes (4a, 4b and 4c), respectively. Analysis of the spectroscopic data revealed the presence of a methylenediketopiperazine moiety in E-7, E-8, and E-10. Based on these informations, the structures 3a, 3b, and 3c were assigned to E-7, E-8, and E-10, respectively. These three alkaloids were synthesized by condensation of indole-3-carbaldehydes (4a, 4b, and 4c) with methylenediketopiperazine (5). The stereochemistry of E-7, E-8, and E-10 were determined as shown in the structures. A possible rationalization to explain the isopentenylation in the echinulin-neoechinulin alkaloid biosyntheses was presented.