Structure elucidation and validation of small molecules: the LSD and CASA software
22/10/2013 - Room C209 at 14:00 - External Seminar
(University of Reims (France))
The validation of a molecular organic structure on the basis of 1D and 2D HSQC, COSY and HMBC NMR spectra is proposed as an alternative to the methods that are mainly based on chemical shift prediction. The CASA software was written for this purpose. The matching of the published structure with the NMR data of a triterpene unexpectedly leads to suppose that the reported structure was incorrect. The LSD software was used to find an alternative structure that improved the 2D NMR data interpretation and the carbon-13 chemical shift matching between experimental values and those produced by the nmrshiftdb2 prediction tool.
The LSD software proposes the structures of small organic molecules that fit with structural constraints from 1D and 2D NMR spectroscopy. Its initial design introduced limits that needed to be eliminated in order to extend its scope and help its users choose the most likely structure among those proposed. The LSD software code has been improved, so that it recognizes a wider set of atom types to build molecules. More flexibility has been given in the interpretation of 2D NMR data, including the automatic detection of very long-range correlations. A program named pyLSD was written to deal with problems in which atom types are ambiguously defined. It also provides a carbon-13 NMR chemical shift-based solution ranking algorithm. PyLSD was able to propose the correct structure of hexacyclinol, a natural product whose structure determination has been highly controversial. The solution was ranked first within a list of ten structures that were produced by pyLSD from literature NMR data.