Structure elucidation of small organic molecules by contemporary computational chemistry methods

Small molecules derived from natural sources such as plants, fungi, bacteria, or synthetic materials have served as promising drug candidates for a long time. Unambiguous determination of chemical structures of these natural/synthetic molecules is a prerequisite for their development into new drugs. Despite the significant development of modern analytical tools it is still challenging to accomplish full structural assignment. In the last decades, computational chemistry methods using quantum mechanics and molecular mechanics theories followed by sophisticated statistical approaches have been rapidly developed. Such in silico platforms have widely and successfully been used to characterize and revise the structures of natural/synthetic products. In this review, we summarize contemporary computational approaches coupled with statistical methods for structure elucidation of small organic molecules. Among these approaches available, we opted for several relevant case studies in which the stereochemistry/structures of natural products were elucidated using these combinatorial methods.