A milestone in Nature's organic "molecular editing"

In a landmark achievement reported in Nature on August 9, 2022, chemists from the Scripps Research Center and the University of California, Los Angeles have developed a precise, flexible, and powerful new method for modifying a class of compounds known as Compounds of bicyclic azaarenes, which reflect an easier and more flexible molecular design, allow chemists to synthesize countless previously unattainable chemical products, including potentially blockbuster drugs

"These new methods effectively provide chemists with a unified, practical, late-stage 'molecular editing' toolkit to modify bicyclic aza-arenes at desired sites in any desired order.

Yu and his lab collaborated on the research with the lab of Kendall Houk, Ph.

Building organic molecules using laboratory chemistry techniques, known as organic synthesis, has always been more challenging than building things on a macro scale

The ambitious goal, or "holy grail," of many synthetic chemists has been to develop flexible and versatile molecular editing methods that modify as many carbon atoms as possible in any position by breaking carbon-hydrogen bonds in the starting molecule

The new approach has turned that dream into a reality, at least for the most common class of starting molecules used by medicinal chemists

These new methods are variants of the CH (hydrocarbon) functionalization method: remove a standard hydrogen atom from a carbon atom and replace it with a more complex set of atoms

"A key aspect of our new approach is that the template-direct CH functionalization is not based on traditional electronic criteria, but on the path-to-target distance and geometry," Yu said

Zhoulong Fan, Xiangyang Chen, Keita Tanaka, Han Seul Park, Nelson YS Lam, Jonathan J.