Selective Entry to the Dimeric or Oligomeric Pyridinium Sponge Macrocycles via Aminopentadienal Derivatives. Possible Biogenetic Relevance with Manzamine Alkaloids

• Published in: Journal of the American Chemical Society 1998-08, Vol.120 (32), p.8026-8034
• Main Authors: Kaiser, Alexander, Billot, Xavier, Gateau-Olesker, Alice, Marazano, Christian, Das, Bhupesh C
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9805369

A general entry to dimeric or oligomeric pyridinium macrocycles related to natural products 2 and 3, recently extracted from sponges, is reported. A series of 3-(ω-aminoalkyl)pyridines 6a − c has been synthesized first. The Zincke synthesis of pyridinium salts starting from such derivatives opened a new and efficient route to cyclic dimer 11 and natural cyclostellettamine B. It allowed, in addition, the highly selective syntheses of oligomers 18 and 21 and of the corresponding macrocycles, tetramer 23 and octamer 25. These results suggest a plausible pathway for the biosynthesis by sponges of 3-alkylpyridine and pyridinium alkaloids (1−3). The newly contrived biogenetic hypothesis focuses on the chemistry of aminopentadienal derivatives, very likely to be obtained from the condensation of malondialdehyde and long chain aminodialdehydes, all these natural intermediates being derived from the metabolism of fatty acids. The possible involvement of such reactive species in the biogenesis of manzamine A and related alkaloids is also discussed. Some features of the biological activity of the natural and synthetic products are briefly presented.