Chapter 7: Alkaloids I

Historically, alkaloids were defined by their alternating solubilities in acidic aqueous solutions, as amine cations, and in organic solvents, as neutral amines, allowing early purification of otherwise unrelated scaffolds, driven by the protonation/deprotonation equilibria. Some 27 000 alkaloid natural products have been purified and characterized, with structures ranging from coniine to caffeine, piperine, quinine, morphine, scopolamine, tubocurarine, and strychnine. Amino acids are the building blocks for common classes of alkaloids, such as those listed above, by early decarboxylation to amines for further complexity generation. The identity of the amino acid precursor is one basis for mechanistic classification of alkaloid subfamilies. Another is the type of nitrogen-containing ring systems in alkaloid products, including pyrrolidines, tropanes, and pyrrolizidines from ornithine; quinolizidines and indolizidine from lysine; isoquinolines from phenylalanine and tyrosine; quinazoline and quinolines from anthranilate; and indole alkaloids from tryptophan. Representative biosynthetic routes to these alkaloid heterocycles, lysergic acid, ergotamines, indolocarbazoles, and strictosidine, as well as recent elucidation of the route to colchicine, are delineated.