Chapter 1 Biosynthesis of Pyrrolizidine and Quinolizidine Alkaloids

Abstract

This chapter discusses the structure, biological activity, and biosynthesis of pyrrolizidine alkaloids, and quinolizidine alkaloids. Pyrrolizidine alkaloids contain a base portion (necine), with hydroxy groups generally present at the 1- and 9-positions. The alkaloids are usually present in plants as ester derivatives, such as echinatine. Many pyrrolizidine alkaloids exhibit a range of biological activities, particularly hepatotoxicity, and many livestock deaths result from ingestion of plant material containing pyrrolizidine alkaloids. These alkaloids also contribute to human liver disease, when they are consumed by humans, either by accident when foodstuffs are contaminated, or deliberately through injudicious use of herbal remedies prepared from plants known to contain pyrrolizidine alkaloids. The use of 13 C, 15 N-doubly labeled precursors shows that the pathways to retronecine and lupinine are fundamentally different. The routes to retronecine and the other necines are characterized with a series of well-defined intermediates; however, details of the processes involved in the construction of lupinine and the tetracyclic quinolizidine alkaloids are poorly understood.