ABSTRACT
Indole alkaloids constitute an important class of natural products that includes a large number of pharmacologically important substances such as antitumor alkaloids (vinblastine, vincristine, reserpine, and ajmaline), blood pressure lowering substances (reserpine), an alkaloid (ajmaline) used to treat cardiac arrythmias, and the hallucinogen lysergic acid and its derivatives. Some of the indole alkaloids are strongly toxic (strychnine) or psychoactive substances (psylocibine, bufotenin). These compounds belong to one of the largest groups of secondary metabolites, comprising different structures often with remarkable complexity. Indole is an aromatic heterocyclic organic compound (Figure 29.1). It has a bicyclic structure, consisting of a six-membered benzene ring fused to a ve-membered nitrogen-containing pyrrole ring. Indole alkaloids are biogenetically derived from tryptophan. These alkaloids contain two nitrogen atoms, one of which is contained within the vemembered part of the indole nucleus. Alkaloids such as quinine and camptothecin and its derivatives, with a ve-membered heterocylic ring that is expanded by the inclusion of an extra carbon, are classied as quinolines rather than indoles, although their biogenic origins are the same. The diversity of alkaloid structures forced scientists to concentrate during recent years on the elucidation
29.1 Denition, Chemistry, and Classication of Indole Alkaloids ........................................... 731 29.2 Occurrence and Medical Signicance of Indole Alkaloids ................................................ 732 29.3 Sample Preparation for HPLC Analysis ............................................................................. 742 29.4 Sample Purication and Concentration .............................................................................. 744 29.5 HPLC Analysis of Indole Alkaloids ................................................................................... 745
29.5.1 Normal-Phase System ........................................................................................... 745 29.5.2 Reversed-Phase System ......................................................................................... 750
29.5.2.1 Mobile Phases at Low pH..................................................................... 750 29.5.2.2 Mobile Phases at High pH .................................................................... 751 29.5.2.3 Ion-Pair (IP) Systems ........................................................................... 753 29.5.2.4 Mobile Phases with Addition of Silanol Blockers ................................ 753
29.5.3 Chiral Separations ................................................................................................. 754 29.5.4 Coupled Techniques .............................................................................................. 755 29.5.5 Quantitative Analysis ............................................................................................ 755
29.6 Details of Separations of Particular Types of Indole Alkaloids ......................................... 757 29.6.1 Simple Indoles (β-Carboline Alkaloids) ............................................................... 757 29.6.2 Ergot Alkaloids ..................................................................................................... 758 29.6.3 Terpenoidal Indole Alkaloids ................................................................................ 760 29.6.4 Indoles with a Quaternary Nitrogen ...................................................................... 761 29.6.5 Other Indole Alkaloids .......................................................................................... 761
References ...................................................................................................................................... 761
of biosynthetic pathways at the enzymatic level. Thus, during the last few years, a highly successful study of the molecular genetics of alkaloid formation has been undertaken, including the rst examples of heterologous expression of appropriate enzymes catalyzing alkaloid metabolism.
