New observations on the secondary chemistry of World Ephedra (Ephedraceae)

For several millennia, stem extracts of Ephedra (Ephedraceae, Gnetales) hav e been used as folk medicines in both the Old and New World. Some species w ere used in treatments of questionable efficacy for venereal disease in Nor th America during the last century. Many Eurasian species produce phenyleth ylamine alkaloids, mostly ephedrine and pseudoephedrine, that interact with adrenergic receptors in the mammalian sympathetic nervous system. Asian Ep hedra have been used recently in the clandestine manufacture of a street dr ug, methamphetamine. Although ephedrine alkaloids are not detectable in New World species of Ephedra, together with Asian species they contain other n itrogen-containing secondary metabolites with known neuropharmacological ac tivity. Many mesic and particularly xeric species worldwide accumulate subs tantial amounts of quinoline-2-carboxylic acids, or kynurenates, in their a erial parts. Many species of Ephedra accumulate cyclopropyl amino acid anal ogues of glutamate and proline in their stems and roots, and particularly i n the seed endosperm. Mesic species synthesize substantial amounts of three L-2-(carboxycyclopropyl)glycine stereomers rarely seen in nature. A cyclop ropyl analogue of proline with known antimicrobial activity, cis-3,4-methan oproline, is found in large amounts in the stems and seeds of many Ephedra species. The ability to synthesize cyclopropyl amino acids may be an ancest ral feature in the taxon. The natural function in the taxon of these three groups of secondary compounds remains to be established.