Journées RMN grand SUD, June 11-12, 2018 | ACD/Labs
ACD Labs Logo

Journées RMN grand SUD

June 11-12, 2018
amphi Gallais CNRS campus of IPBS and LCC, Toulose, France

Poster Schedule

Generating Unbiased Structural Alternatives for Automated Structure Verification
Sergey Golotvin, Rostislav Pol, Mikhail Elyashberg, Dimitris Argyropoulos and Karim Kassam

Abstract: Automated structure verification (ASV) using NMR data is gaining acceptance as a routine application for qualitative evaluation of large compound libraries produced by synthetic chemistry. A proposed structure is confirmed if it fits a number of conditions from 1D 1H NMR data [1] or from a combination of 1D-1H and HSQC data.

Although it is easy to conclude that a proposed structure does not pass this “NMR filter” it is not trivial to guarantee the opposite—that a proposed structure passing this filter is the correct one. There is always a possibility that an isomeric structure fits the same NMR data better than the proposed structure. One way to decrease the possibility that false structures will pass is to use as many NMR experiments as possible for structure validation (1D-13C, HMBC, etc.). Another method [2] is to bring in and simultaneously verify several structures isomeric to the proposed. This concurrent structure verification enables structural differences to be highlighted through gradual tightening of NMR prediction tolerances until only a single structure remains.

The similarity of isomeric structures to the proposed structure means that spectral interpretation is biased by the chemist’s expectations and may result in false positives.

Here we present a method for generating alternative ‘unbiased’ structures for ASV, based on the structure generator [3] used in a CASE system. Using this approach we are able to generate all isomers that fit a particular NMR dataset without using any prior available knowledge. Practical aspects of this ‘unbiased’ verification are discussed and several examples are shown.

  1. Golotvin, Sergey S., Vodopianov, Eugene, Pol, Rostislav, Lefebvre, Brent A., Williams, Antony J., Rutkowske, Randy D., Spitzer, Timothy D., Mag. Res. Chem. 45(10), 803-813, 2007.
  2. Golotvin, Sergey S., Pol, Rostislav, Sasaki, Ryan R., Nikitina, Asya, Keyes, Philip, Mag. Res. Chem. 50(6), 429-435, 2012.
  3. Elyashberg, Mikhail E, Williams, Antony J., Blinov, Kiril.A., “Contemporary computer-assisted approaches to molecular structure elucidation”, RSC, Cambridge, 2012