Yale lab finds new ways to synthesize HIV inhibitor

A team of chemists from Yale University have discovered a new way to synthesize an organic compound capable of inhibiting HIV, and their technique could save time by streamlining the entire process, according to research published Wednesday in the journal Nature.

The new method, which was developed by Yale chemistry professor Seth Herzon, postdoctoral associate Brendan Parr, and graduate student Christos Economou, manufactures nitrogen-based alkaloids without requiring the typical tempering of the element’s reactive tendencies.

“In this approach we start from stable (aromatic) nitrogen precursors, which are inexpensive, easy to manipulate, and readily-converted to the desired compound,” Herzon told redOrbit via email. “Prior approaches to these types of alkaloids employed non-aromatic nitrogen precursors and required many more steps to reach the final compound.”

Technique could be adapted to cancer-fighting compounds

Using a new type of starting materials, the Yale team was able to unmask nitrogen in the final step of the process to use a new approach that speeds up the synthesizing process. The result is a manufactured version of batzelladine B, an anti-HIV chemical naturally found in red sponges in the Caribbean.

Batzelladine B has shown promise as an inhibitor of HIV viral entry, one of the first steps in the development of infections involving the AIDS-causing virus, the study authors explained. Using a less reactive material called aromatic nitrogen heterocycles as a launch point, they were able to pursue multiple complex reactions in just one single step of the process.

Furthermore, Herzon said that the process could also be adapted to synthesize other compounds, including anti-cancer, anti-microbial, and other anti-HIV compounds. He told redOrbit that there are at least 12 distinct alkaloids he could easily access using this approach and that they are currently in the process of adapting the technique to do just that.

“Natural products are an excellent starting point for drug development,” Herzon said. “Over a third of all drugs approved from 1990-2011 were natural product-based, but their structural complexity usually renders their synthesis rate-limiting. My laboratory aims to overcome this by developing innovative, efficient, and generalizable strategies to prepare natural product targets.”

—–

Feature Image: Yale