Validation of Structural Proposals by Substructure Analysis and ¹³C NMR Chemical Shift Prediction

Abstract

The 2D NMR-guided computer program COCON can be extremely valuable for the constitutional analysis of unknown compounds, if its results are evaluated by neural network-assisted 13C NMR chemical shift and substructure analyses. As instructive examples, data sets of four differently complex marine natural products were thoroughly investigated. As a significant step towards a true automated structure elucidation, it is shown that the primary COCON output can be safely diminished to less than 1% of its original size without losing the correct structural proposal.

15N NMR Spectroscopy in Structural Analysis: An Update (2001 - 2005)

“…Based on nine different neural networks, the C_SHIFT program [252,253] was shown to be able to predict the 13 C NMR chemical shifts of all organic compounds that contain exclusively H, C, N, O, P, S, and the halogens. The applicability of COCON combined with neural network-assisted 13 C NMR chemical shift and substructure analyses for the constitutional analysis of unknown compounds was further investigated with data sets of four differently complex marine natural products [254]. Three new approaches for the automated elucidation of structure, based on 13 C NMR spectroscopy and applying a neural network to predict the carbon chemical shift and rank the results of structure generators according to the agreement between the experimental and predicted chemical shifts, were introduced recently.…”

Simulation of 13C nuclear magnetic resonance spectra of lignin compounds using principal component analysis and artificial neural networks

“…Artificial neural networks (ANNs) have been reported for use in a few analytical chemical studies including 1 H NMR [15] and 13 C NMR spectroscopy [16][17][18][19][20][21]. To ensure the robustness and generality of an ANN model, various types of descriptors should be used as its input.…”

Novel methods of automated structure elucidation based on 13C NMR spectroscopy

“…20c, 21 Also, constitutions that yield a r.m.s.d. value below the experimental deviation plus the standard deviation of the prediction method are treated as potentially correct constitution of the unknown compound.…”

“…This information can be lists of necessary (good list) or forbidden (bad list) fragments applied in MOLGEN or GENIUS, which can be known from synthesis, experience or additional experimental data. 21 The COCON algorithm 20,24 is specialized to exploit two-dimensional NMR connectivity information, which drastically reduces the size of the structural space spanned by one molecular formula. Thus, the structural space to be generated is restricted to all structures that meet the experimental connectivity information.…”

“…The ranking within this subspace is again obtained by computing the 13 C NMR chemical shift values 20c with C SHIFT. 21 COCON also allows including information from other sources as fixed bonds or forbidden bonds. This corresponds to the good list and bad list philosophy.…”