CHEMISTRY, OCCURRENCE AND BIOLOGICAL EFFECTS OF SATURATED PYRROLIZIDINE ALKALOIDS ASSOCIATED WITH ENDOPHYTE GRASS INTERACTIONS

Saturated amino pyrrolizidine alkaloids with an oxygen bridge between C-2 and C-7 have been isolated from grasses and the chemistry and biol ogy of these substances are reviewed in this paper. These substances a re commonly referred to as loline alkaloids as they are derivatives of loline and originally were isolated from Lolium spp. The saturated am ino pyrrolizidine alkaloids are not hepatotoxic and must be distinguis hed from the 1,2-unsaturated pyrrolizidine alkaloids which are very si gnificant animal and human toxins and carcinogens of plant origin. Che mical synthesis of loline has been achieved based on starting material s of a nitrone and methyl 4-hydroxycrotonate. N-formylloline is made b y addition of ethyl formate to loline and removal of excess ethyl form ate and ethanol formed. N-acetylloline is synthesized by addition of a cetyl chloride to loline in chloroform. N-acetylloline is partitioned into a dilute acid, then from a dilute base with CHCl3, and the CHCl3 removed to yield N-acetylloline. N-methylloline, norloline, N-formylno rloline, N-acetylnorloline, and N-propionylnorloline are also readily formed from loline. Little is known about the biosynthesis of the loli ne alkaloids but from biosynthesis of other pyrrolizidine alkaloids a proposed biosynthesis is ornithine --> putrescine --> spermidine --> - -> dialdehyde --> --> norloline --> --> loline. Loline was first isola ted from Lolium temulentum L. (Lolium cuneatum Nevski) and later sever al derivatives were identified in tall fescue (Festuca arundinacea Sch reb.). Chromatographic methodologies have been used to separate the py rrolizidine alkaloids but 50-m capillary columns (0.32 mm i.d.) or 10- m wide-bore columns (0.53 mm i.d.) provide the greatest resolution of the many loline derivatives. Loline alkaloids have been found primaril y in plants known to be infected with Acremonium coenophialum Morgan-J ones and Gams. Lolines have been found in Lolium perenne L., F. arundi nacea, and Poa autumnalus Muhl. ex Ell. infected with A. coenophialum and in Festuca gigantea (L.) Vill. infected with an unidentified Acrem onium spp. Loline alkaloids were present in infected tall fescue in gr eatest amounts in seed, followed in decreasing amounts in the rachis, stem, leaf sheath, and leaf blade. Site of synthesis, plant and/or end ophyte, is not known nor is the translocation tissue known. During the main part of the growing season there is little change in the accumul ation of the loline alkaloids in leaf blade. Alkaloid levels increased with plant age and increased in regrowth tissue. The concentration of endophyte mycelium in leaf sheaths is Positively associated with loli ne alkaloid accumulation. N-formylloline is toxic to several different insects from ingestion, topical and injected applications. Larger ani mal bioassays have not been conducted with pure compounds but the obse rvations suggest some pharmacological activity in these systems.