Synthesis of Loline Alkaloids

Hello all. My name is A.J. Wright and I am a junior chemistry major at the college. This summer I will be working in the natural products synthesis lab of Professor Jonathan Scheerer. This will be a continuation of a project that I began contributing toward last summer and throughout the current academic year. I am attempting a total synthesis of loline alkaloids, which are natural compounds made by fungal endophytes that live in certain types of grass. These are of human interest because they have insecticidal, insect anti-feedant, and other functional properties. Providing an efficient synthetic route of these compounds could have huge implications for agriculture, albeit such progress is decades away. We also hope to gain more knowledge of the mechanism by which they are produced in the fungus. To this end, we plan to synthesize a potential biological intermediate and provide it to colleagues who are investigating loline biosynthesis.

The project has proved challenging and rewarding in the past. I look forward to putting my full effort into the lab this summer without the added stresses of of academic courses. I’m also more confident with my added lab skills and experiences, whereas last year I was completely new to independent research. In all, I’m very excited for the future and look forward to reading about everyone’s work.

Abstract

An asymmetric total synthesis towards the  loline alkaloids is proposed. Loline alkaloids are metabolites produced by fungal endophytes in loline grass. The compounds exhibit a strained ether-bridged pyrrolizidine skeleton, and have insecticidal, insect antifeedant, and antitumor properties.  Central to the current synthesis is a Petasis-Borono Mannich reaction with a commercially available vinyl boronate substrate to establish a carboxybenzyl protected enol. A ring closing methasis (RCM) reaction will also be employed to establish the ether bridge and bicyclic core structure. An elucidation of loline biosynthesis will be attempted by synthesizing a potential biological intermediate for further feeding studies in the fungus.