Natural products and their derivatives continue to provide a novel source for medicinal compounds used to combat illnesses including cancer, malaria, and Alzheimer’s. In modern applications, the pharmaceutical industry commonly utilizes the structure of natural products as models on which combinatorial chemistry and molecular biology can be applied. NMR measurement of 1JCC coupling by 2-D INADEQUATE allows for efficient structure elucidation in hydrogen poor compounds and can be measured in a single experiment at natural 13C abundance. Additionally, modern DFT computations of model compounds are functionally accurate with B3LYP/EPR-III 1JCC calculations correlating with experimental data. By combining theoretical predictions with experimental INADEQUATE 1JCC coupling values, challenging structural problems can be solved. 5-methylmellein, a DNA Polymerase l inhibitor, hydroheptelidic acid, which displays antitumor and antimalarial activity, and austrocortinin, an anthraquininoid pigment, are three natural products extracted from endophytic fungi found in the Central Florida area with potential medical applications. Structural elucidation of these compounds was performed in order to evaluate the accuracy of this concerted model; particularly, by aiming to solve difficult structural motifs including strong intramolecular hydrogen bonding, verifying heteroatom identity, assigning double bond configuration, and assigning the correct tautomeric form. In all cases, the structural ambiguities were resolved and single best-fit structures were uniquely identified; verifying that such motifs can be accurately modeled.

Solving challenging structural motifs in natural products using concerted DFT modeling and 2-D INADEQUATE NMR

253rd National Meeting (2017)

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