Efficient workflow for structural elucidation applied to solidagenone derivative: Combining the speed of ML-J-DP4 screening with the precision of DP4+

Abstract

The derivatization of solidagenone through ring expansion, using the "Complexity to Diversity" synthetic strategy to obtain polyketones, yielded two products upon reaction of an intermediate with in situ-generated ruthenium tetroxide. As might happen, the spectroscopic and spectrometric data were inconclusive for the structural determination of one of these products. To address the issue, a ML-J-DP4//DP4+ workflow was studied, which allowed simultaneous determination of connectivity and relative configuration with high accuracy, while saving computational resources. Furthermore, during the calculation of NMR data at the DP4+ level, abnormally large errors were observed for the beta carbon of a polyhydroxylated conjugated enone. A literature analysis revealed that this behavior could be generalized, and after careful examination, it was determined to be the result of small geometric distortions caused by an overestimated network of intramolecular hydrogen bonds. To mitigate this common source of discrepancy, a heuristic solution was introduced as a proof of concept by in silico blocking of hydroxyl groups.