ISOLATION, STRUCTURE ELUCIDATION, AND SYNTHESIS OF NOVEL HYDROXYLAMINE-CONTAINING POLYAMINES FROM THE VENOM OF THE AGELENOPSIS-APERTA SPIDER

Novel hydroxylamine-containing polyamines have been isolated from the venom of Agelenopsis aperta, a funnel-web spider found throughout the western United States. 1H and 13C NMR in concert with UV spectroscopy provided important structural inputs particularly for determining the aromatic chromophores. Fast-atom bombardment (FAB) mass spectrometry, however, provided the key data for establishing the polyamine functionality of Agel 489 (1), 505 (2), 452 (3), 468 (4), and 448 (5). These polyamine structures were confirmed by total synthesis. The recurring propylamine portions of the polyamine chains were assembled by amine cyanoethylation followed by nitrile reduction. Hydroxylamine incorporation was best achieved via a two-step sequence involving amine oxidation with 2-(phenylsulfonyl)-3-phenyloxaziridine followed by sodium cyanoborohydride reduction of the nitrone products. TFA and/or dioxane/HCl treatment of the rm-butoxycarbonyl (BOC) and methoxymethoxy (MOM) protected intermediates provided the natural Agelenopsis hydroxylamine products 1-5 as their acid salts. In the HCl-mediated removal of the protecting groups to generate 4-hydroxyindoleacetamides 2 (Agel 505) and 5 (Agel 448), intermediate 1-carboxyl-3-indoleacetamides were isolated. © 1990, American Chemical Society. All rights reserved.