New Methods and Strategies for Complex Molecule Synthesis

Lawrence Williams, from the Rutgers University chemistry & chemical biology department, came to Dartmouth College this past Thursday to discuss structure space, natural compounds, and allene oxidation as a new method for complex molecule synthesis. Williams is regarded as a pioneer in the chemistry of allenes. He has developed techniques to make and use allenes.

Allenes are a subset of molecules of particular interest due to their chirality. Chirality refers to the fact that allenes have a non-superimposable mirror image, much like our left and right hands. Williams has published multiple papers on allene chemistry.

To begin his discussion on new methods and strategies for synthesizing complex molecules, Williams noted that it is common in medicinal chemistry to consider the structure space of a molecule. In his estimations, one can use an ellipsoid to capture the molecule as a simplistic model of the structure space of a molecule. While he usually considers structure space when synthesizing compounds, he mentioned that structure space is one key characteristic that many other chemists tend to ignore.

Williams also stressed the importance and abundance of chemicals that appear in nature. Xenia diterpenoids, he said, exhibit particularly great structural diversity and promising bioactivity. However, he also posed the question of why chemists focus attention on natural products in the first place. If chemists can identify the compound, then they already know its structure and activity. So what could possibly be gained from making related compounds? The simple answer is that perhaps the structure can in some way be improved and developed.

Chemists study natural products because it has been found that many natural compounds have medicinal uses. Natural compounds tend to be relatively complex, though that opens up the possibility for more variations in structure. Williams also stated that studying these complex natural compounds increases our understanding of structure, reactivity, and function.

Finally, Williams discussed his implementation of allene oxidation as a method for synthesizing new and novel compounds. When Williams first started research, there were only about ten reports on spirodiepoxides, an allene derivative. He admitted to beginning research on spirodiepoxides out of despiration, hoping that one day they would hit it big. Williams now applies his methods developed from his research on spirodiepoxides to synthesis reactions involving another compound, erythromycin, an antibiotic.

In the end, when considering structure space of a molecule, Williams has successfully implemented allene oxidation to the synthesis of novel, complex molecules. His contributions to the field of chemistry are immense and will continue to grow.