Research in the Scheerer lab is directed toward two
primary research areas that fall broadly under the umbrella of natural
products. One project centers on the [2.2.2]-diazabicyclic indole alkaloids,
a class of natural products with diverse bioactivities, significant therapeutic
potential, and interesting biosynthetic questions. The [2.2.2]-diazabicyclic
structural motif common to these alkaloids is postulated to arise through a
biogenic intramolecular hetero-Diels-Alder cycloaddition. Although precedented
in nature, very little is known about this cycloaddition variant more
We have been investigating several of the fundamentals of this reaction and have developed synthetic methods for diastereoselective cycloaddition starting from a chiral non-racemic diketopiperazine core.
Synthesis and Biosynthesis of Loline Alkaloids
My other main research area centers on the loline alkaloids and related bioactive pyrrolizidine alkaloids. Several species of common grass (e.g., rye, fescue) harbor mutualistic fungi. In return for nutrients from the plant, these fungal endophytes produce loline alkaloids, which possess insecticidal and antifeedant activities that protect the plant from insect herbivory. This relationship is a natural pest control paradigm that has existed for millions of years. Because of low mammalian toxicity, there is potential to use lolines as natural commercial insecticides. The main objectives of this project area are twofold: (1) to develop an efficient, general and direct synthesis of the loline alkaloids and (2) investigate the biosynthesis of these alkaloids.