Loline alkaloid

Lolinalkaloide, also briefly called lolines, are counting on the alkaloids bioactive natural products. Lolinalkaloide are especially produced by symbiotic fungi on grasses from the family of ergot fungus relatives. They act as natural insecticides and serve both the fungus and the host plant as a defense mechanism. Chemically include Lolinalkaloide with their 1- amino-2 ,7- Epoxypyrrolizidinstruktur to the pyrrolizidine alkaloids.

Occurrence

Lolinalkaloide can especially in grasses, in particular representatives of the genera Lolium, Festuca and Poa be found. But not the plant, but an infection with endophytic fungi of the genus Epichloë (and its known as Neotyphodium anamorphs ) of the family of the ergot fungus relatives is responsible for the production of these alkaloids.

Outside the symbiotic community of sweet grass and endophyte come Lolinalkaloide only sporadically in nature. (: Legume family) and Argyreia mollis ( Family: bindweed ) How about an occurrence of Lolinalkaloiden in Adenocarpus hispanicus been reported.

Biosynthesis

Despite their structural affiliation to the group of pyrrolizidine the biosynthesis of Lolinalkaloide differs significantly from that of other pyrrolizidine alkaloids. Lolinalkaloide derive unlike other pyrrolizidine not from ornithine or arginine from, but are formed from the amino acids proline and homoserine. The primary biosynthetic 1- Acetamidopyrrolizidin is formed, which is cyclized to Acetyltemulin. More Lolinalkaloide derived biosynthetically from this substance. The biosynthesis of the various enzymes of the LOL Lolinalkaloide gene cluster are involved.

Chemistry

Structure

Lolinalkaloide are tricyclic pyrrolizidine alkaloids. The members of this class differ based on the substituents on the amino group in position 1 of the Lolingrundgerüsts. The structurally simplest Lolinalkaloide are Temulin with a free amino group and its N- methylated derivative Lolin. The other Lolinalkaloide derived from these substances and carrying various acyl substituents.

Synthesis

For the synthesis of Lolinalkaloiden various methods are described.

The Lolinalkaloidsynthese described by Wilson is based on 8- oxabicyclo [3.2.1 ] oct -6 -en- 3-one, which is reacted in several steps to the 9- oxa -4- azabicyclo [ 4.2.1 ] non -7-ene. An intramolecular ring linking in the presence of bromine leads to 2,7- Epoxypyrrolizidin -1 - bromide, which can be aminated to Temulin or other Lolinalkaloiden.

Starting from 1- ethylpyrrolidine -3-one according to Cope elimination takes place to give the corresponding nitrone under cycloaddition reaction of (E)- methyl 4- hydroxy-2- butenoate of the intermediate ring closure to hexahydropyrrolo [1,2- b] [ 1,2] oxazole derivative, which is rearranged in terms of a SN2 reaction to Pyrrolizidinderivat after reduction of the NO bond. A Williamson ether synthesis allows the conclusion of the tetrahydrofuran ring. Lolin as the end product of the pathway being obtained by Curtius rearrangement followed by reduction of the intermediate 2,7- Epoxypyrrolizidin -1 carbonsäureethylether.

Another route starts from Divinylcarbinol and 3- butenylamine and ring closure of the Heyahydroazocinderivat. After azidation with lithium azide transannular ring link to Pyrrolizidinderivat occurs in the presence of bromine in terms of a combination of electrophilic and nucleophilic substitution mechanisms as the key step of the synthesis. Of tetrahydrofuran is then closed by an intramolecular etherification. The resulting 2,7 - Epoxypyrrolizidin -1 - azide reduced to Temulin or methylated Lolin and be reduced.

Biological Significance

Lolinalkaloide addition to the ergot alkaloids, Lolitremen and Peramin a component of the food safety of the symbiotic community of endophytes of the genus Epichloë / Neotyphodium and grasses. Lolines have an insecticidal effect on a broad spectrum of insects.