Chemists at the University of Iowa have designed and demonstrated a new approach to spatially configuring chains of atoms in a natural compound that may have medical uses.

The team, led by Gregory Friestad, associate professor in Department of Chemistry, performed the chemical modifications to synthesize 1,5 polyols, part of a class of natural products known as polyketides.

Polyketides are a group of secondary metabolites, or substances formed in or necessary for metabolism, with remarkable diversity in structure and function.  Polyketide natural products are known to possess pharmacologically important attributes, including antimicrobial, antifungal, antiparasitic, antitumor, and agrochemical properties.

A challenge is modifying them so they can be used for medical and other applications. With 1,5 polyols, the main obstacles have been to determine the compounds’ chirality, the left- and right-handed spatial orientation of oxygen atoms relative to carbon atoms, and to synthesize them with control over the chirality.

In one published study, Friestad’s team introduced a new strategy that establishes the oxygen orientations earlier, placing them within smaller “configuration-encoded” building blocks. The new approach allows chemists to create any desired combination of left- and right-handed orientations.

In an accompanying paper, a group of graduate and undergraduate researchers, led by graduate student Ryan Friedrich, demonstrated the application of this approach in a synthesis of the 1,5-polyol components of tetrafibricin, a compound that interferes with blood clotting and offers potential for development of future anti-thrombotic drugs.

The two companion papers were each selected as Featured Articles by the Journal of Organic Chemistry and appear in the Nov. 16, 2018, issue.