Aspergillimide

The syntheses and biosyntheses of the paraherquamide and brevianamide families of prenylated indole-derived alkaloids are reviewed. It has been proposed that the unique bicyclo[2.2.2]diazaoctan ring system that is common to this family of natural products, arises by a biological intramolecular Diels-Alder cycloaddition reaction. Both synthetic approaches and total syntheses of several members of this family of natural products are reviewed. The biosynthesis of these alkaloids has also constituted an active area of research and the current state of knowledge on the biosynthesis of these natural products are reviewed.

2,6,6-Trimethyl-2-azaspiro[4.4]nonane-1,3-dione (9), a spirosuccinimide moiety of asperparaline A (1), was synthesized by starting from 2,2-dimethylcyclopentanone (4) via trinitrile 6 in five steps in a moderate yield. This conversion establishes a model study for synthesis of the spirosuccinimide moiety of asperparaline A (1).

The primary amino acid building blocks that constitute asperparaline A have been determined through feeding and incorporation of 13C-labeled intermediates. The beta-methyl proline residue is constituted from (S)-isoleucine, the novel spiro-succinime moiety is derived from the oxidative degradation of (S)-tryptophan, and (S)-adenosylmethionine contributes the two N-methyl residues. In addition, it was found that the incorporation of 13C-labeled acetate into the single isoprene unit clearly demonstrates that the isoprene moiety is derived from the mevalonate pathway.