Design and Cost-effective de novo Synthesis of Aza-artemisinins

In this project, the researchers designed aza-artemisinins (ARTs) by replacing a carbon on the skeleton into a nitrogen in order not only to gain a more facial access to the pharmacophore but also to improve the aqueous solubility and increase structural diversity that may be sufficient to overcome ART-resistant ring stages.

As a notable feature of the drug design, the small change on atomic level, replacing a single carbon of the ART skeleton with a nitrogen, opens a new vista for achieving major improvements in production efficiency as well as requisite water solubility. Exploiting versatile reactivity of the nitrogen functional group, we have gained expeditious access to the aza-ARTs through single-step assembly of three building blocks and subsequent manipulations to construct the complex skeleton in a small number of steps.

The team’s approach is expected to drastically simplify de novo chemical synthesis of ART derivatives without modifications of the trioxane core, the key substructure responsible for the potent anti-malarial activity.

Drug Resistance
Drug-based Strategies

Jan 2014

$60,000