Alicia Ross

Computational calculations using quantum chemical methods were used to identify key reaction details in protonated oxidosqualene and protonated squalene mechanisms. These two chemicals are important to the pharmaceutical industry due to their resemblance to steroids. The findings in this work will be applied to similar chemical reactions and used by synthetic scientists to effectively synthesize these important molecules.

Steroids and diterpenoids are produced through enzyme-chaperoned rearrangements with high stereoselectivity and are an important family of natural products relevant to many fields. Mechanistic insight of these polycyclizations and rearrangements can elucidate valuable information on enzyme structure and function and reaction mechanisms which can be relevant to synthetic and mechanistic chemistry fields. Here, the polycyclization reaction of protonated squalene and protonated oxidosqualene was investigated using computational chemistry. Density Functional Theory (DFT) calculations were used to estimate energy levels for a truncated version of these systems’ starting molecules, transition states, and products and were connected through intrinsic reaction coordinate calculations. Ab Initio Molecular Dynamics (AIMD) calculations were then used to probe the dynamics of the mechanisms and investigate its role in the reactivity of these terpenes. It is hypothesized that there is a non-statistical dynamics effect hindering these cyclization pathways or the presence of an entropic intermediate in one or both of these systems.