Reaction mechanism and chemotaxonomy in the formation of the type I indole alkaloids derived from secologanin

The history of biomolecules is written into the structure of their educts and products. The group of indole alkaloids derived from secologanin and tryptamine has more than 2000 individual compounds isolated mainly from the Rubiaceae, Loganiaceae, and Apocynaceae plant families and having strictosidine as a common precursor. To detect their history in its main lines, the compounds isolated from the same or closely related species were ordered as intermediates into reaction sequences according to the principles of basic organic reaction mechanisms. The analysis is restricted to the main lines of the monomeric alkaloids having one un-rearranged secologanin subunit (type I) closed to N-4 atom and one tryptamine subunit in intact or cleaved form. Deglucosylation of strictosidine opens the way for different types of cyclizations. Subsequent key bond-braking and bond-making reactions involve bond C-5-C-6 in the tryptamine subunit, bond C-15-C-16 in the secologanin subunit, and bond C-3-C-7 at the attachment of the two subunits, and indicate the crucial importance of a strong long-range through-bond interaction between the two nitrogen atoms. With a few principles it was possible to interpret such important biogenetic-type steps, as the formation of the akuammidan and akuammilan bridges, the transition from the vincosan into the strychnan and further to the aspidospermatan skeleton, the breaking and transformation of the side-chain of the triptamine subunit and the cleavage of the strategic bond C-15-C-16 toward the formation of the formation of type II and type III alkaloids. The transformations are finely tuned by the stable chirality of C-15, and activation of C-7 and N-4. Fragmentations and rearrangement are important reactions in these transformations, and abundantly supported by chemotaxonomic data based on the Dictionary of Natural Products Database (Version 14.1, 2006, Chapman and Hall/CRC, New York, London, 2005). Copyright (c) 2006 John Wiley & Sons, Ltd.