Neoechinuline: a new indole metabolite from aspergillus amstelodami

Tetrahedron Letters
1969.0

Abstract

The isolation and study of natural compounds having an isoprene moiety attached to an indole system has acquired momentum due to recent research on echinuline and especially ergot alkaloids. We have now isolated a new indole derivative neoechinuline (I) from the same moulds which produce echinuline (Aspergillus Amstelodami), as orange red crystals with mp 237-238° (chloroform) and molecular formula C₂₃H₂₅N₃O₃. It was obtained from the ether extract of dry mycelia via absorption chromatography (silica gel, hexane-ethyl acetate 70/30 vol.). Spectral data included: uv-vis λmax at 230.5 (log ε=4.51), 287 (4.12) and 420 nm; ir (KBr) bands at 3400 (NH), 3200 (NH), 1745 and 1710 cm⁻¹ (CO); mass spectrum with m/e 391 (M⁺), 376 (M⁺-CH₃), 322 (M⁺-C₅H₉) and 69 (C₅H₉⁺); pmr (d₆-DMSO) showing acidic protons at 12.07δ(1H), 11.06 (1H) and 9.59 (1H) (only the last disappears upon addition of trifluoroacetic acid), a 4-proton complex at 6.7-7.5, and two isoprenic units revealed by specific signals. Catalytic hydrogenation (PtO₂, 80 atm., r.t.) of an acetic acid solution of I yielded hydroneoechinuline (mp 216-218° in ethyl acetate, mol. wt 399). Chemical cleavage (permanganate oxidation, hydrogen peroxide oxidation, alkaline hydrolysis) and spectral analyses (uv, ir, pmr, mass) provided evidence for substitution positions and side chain structures. Ozonization of neoechinuline led to isolation of tetraketopiperazine, confirming the 3-substituent structure. The definitive structure I was established for neoechinuline. Neoechinuline is the first natural indole with an isoprenic moiety at position 6, the second instance of dehydrotryptophan, and the second known natural indole with a t-pentenyl residue attached to the indole system.

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