GIAO NMR Calculation-Driven Stereochemical Assignment of Marine Macrolide Natural Products: Assessment of the Performance of DP4 and DP4+Analyses and Assignment of the Relative Configuration of Leptolyngbyalide A-C/Oscillariolide Macrolactone

The stereochemical assignment of marine macrolide natural products by quantum chemical calculations is often hampered by the generation of an intractable number of conformers in molecular mechanics conformation searches. In this study, we assessed in detail the application of GIAO NMR chemical shift calculation and DP4-type statistical analyses to the stereochemical assignment of two marine macrolide natural products, whose relative configurations had been incorrectly assigned in the originally proposed structures. We also examined how DP4+ probability was affected by cumulative Boltzmann population level of molecular mechanics-derived conformers. Finally, GIAO NMR chemical shift calculation/DP4-type statistical analysis was applied to leptolyngbyalide A-C/oscillariolide macrolactone, whose relative configuration has not been assigned so far.

Automated summary

In this study, the application of GIAO NMR chemical shift calculation and DP4-type statistical analyses in the stereochemical assignment of marine macrolide natural products was assessed. The incorrect relative configurations in the originally proposed structures were identified and the effect of cumulative Boltzmann population level on DP4+ probability was examined. Additionally, the GIAO NMR chemical shift calculation/DP4-type statistical analysis was successfully applied to the determination of the relative configuration of leptolyngbyalide A-C/oscillariolide macrolactone.