Calculated NMR Approach Improves Isomer Identification

Using calculated NMR spectra to identify organic stereoisomers has just become easier, thanks to an approach developed by Cambridge University’s Steven G. Smith and Jonathan M. Goodman (J. Am. Chem. Soc., DOI: 10.1021/ja105035r). NMR spectra can be calculated for all diastereoisomers of individual organic compounds, making it possible to identify specific isomers by matching their experimental NMR spectra to calculated ones. But establishing a best fit has been difficult because errors in calculated and experimental spectra make agreement imperfect, even for correct matches. Smith and Goodman have now devised a probability measure called DP4 that works unusually well. They demonstrated the power of the approach by using it to identify the natural product tricholomalide A from 64 possible diastereoisomers. Dennis P. Curran of the University of Pittsburgh comments that he thought “assigning structures by calculating and comparing spectra was for the distant future, but the Smith-Goodman work suggests the future is here. There is potential for broad impact in the synthesis and natural product communities. I could even imagine this becoming a routine tool” that complements other assignment techniques.