Ulven Group

Some say that organic chemists these days can make any molecule. But can they be made easily? Our ideal is to develop practical, safe and environmentally benign synthetic methods where improved methods are needed, with focus on methods that we need in our own medicinal chemistry projects.

Copper-catalyzed N-arylation reactions

Copper is an abundant transition metal that can have excellent catalytic properties under the right conditions. We used copper in combination with a nucleophilic phenanthrolin ligand for the development of an efficient method for arylation of nitrogen in aqueous medium.

(Engel-Andreasen et al. Green Chem. 2013, 15, 336-340)

Simple, safe and stoiciometric production of carbonmonoxide from oxalyl chloride

Carbon monoxide (CO) is a fabulous small building block, but its properties as a highly toxic odorless gas has made many chemists reluctant to bring a cylinder of CO into the lab. Our method makes pure CO in exactly the desired amount easily and cheaply available to anybody with standard equipment and a fume hood.

(Hansen & Ulven, Org. Lett. 2015, 17, 2832-2835)

Synthesis of difficult amides

Amides are everywhere since they link amino acids to form peptides and proteins, and synthesis of amides have often been considered a solved problem. However, most organic chemists have probalby encountered amides that they were unable to synthesize (even if they don’t talk about it…). Electron poor amines such as anilines can be quite difficult substrates for amide coupling, and often impossible if the substrates also are sterically hindered. We encountered one such amide in the synthesis of an FFA2 ligand. We solved the problem by converting the carboxylic acid to a minimally hindered acyl fluoride and performing the coupling with gentle heating. (The challenging nature of this particular amide was illustrated by its clean hydrolysis back to the starting material with only weak acid – in fact, since the FFA2 lignad also contained a carboxylic acid, it was unstable towards itself in neutral form.)

(Due-Hansen et al, Org. Biomol. Chem. 2016, 14, 430-433)

Sonogashira coupling in aqueous media

Our first FFA1 series required assembly by Sonogashira coupling. Unfortunately, the unusually sluggish and unpredictable reactions with our substrate put a serious brake on the progress in the project. This was solved by adopting a ligand published and performing the reaction under aqueous conditions.

Synthesis of functionalized phenanthrolines

Phenanthrolines are efficient metal chelators that have a variety of used. We have used them as scaffolds in design of G-quaruplex stabilizing ligands and as ligands in transition metal catalyzed reactions.

G protein-coupled receptors (GPCRs), also known as 7-transmembrane (7TM) receptors, is the largest class of membrane proteins in the human genome (with ~800 members) and a very important drug target class with 1/3 of current drugs acting on these receptors. Still, only a tiny fraction of the potential is taken advantage of.

Most of our medicinal chemistry projects target GPCRs in one way or another, where we design, synthesize and test new compounds, and aim to make the cycle turn as rapidly as possible to efficiently understand the structure-activity relationship (SAR) and identify compounds with good properties.

We are especially interested in lipid receptors, GPCR dimers as a new potential target class, and receptors that have potential as targets for better drugs for metabolic and inflammatory diseases.

Our body has multiple receptors that detect nutrients and ensure that the body responds appropriately to convert nutrients to energy or use them as building materials. Many of these receptor has potential as drug targets. For example, the medium- and long-chain fatty acid receptors FFA1 and FFA4 are recognized as promising targets for treatment of metabolic diseases such as type 2 diabetes and metabolic dysfunction-associated steatohepatitis (MASH), and activation of the receptors is expected to give the therapeutic effect. This implies that medium and long-chain fatty acids has therapeutic potential through activity on these receptors. Our FFARMED project is set up to explore this potential.