Elucidation by progressive intersection of ordered substructures from carbon-13 nuclear magnetic resonance

Abstract

Computer-asslsted structure elucidation by the DARCIEPIOS system Is descrlbed through practical examples. The search for structures compatible wlth the spectrum, the molecular formula of an unknown compound, and eventual supplementary information Is lnitlalized by dlscrlmlnating lnterpretatlon of these data. Substructures, fully assigned with multlresonance subspectra, are Inferred from the EPIOS knowledge base (EKB). This Interpretatton ellmlnates most of the substructures usually selected by classlcai slngle-resonance methods. Both structural and spectral overlaps between these asslgned substructures lead to a generation graph that contains the candMate structures and their asslgned spectra as subgraphs. The system dynamkally controls the graph search, maklng It heuristlc, by synchronlzlng structure generation with assignment of the query spectrum. Only vaild spectrum/structure solutions are produced by this search.Computer-assisted structure elucidation of unknown organic compounds from their spectroscopic properties is an old but still current project ( I ) . More and more, the analytical potential of 13C nuclear magnetic resonance (13C NMR) and the increasing mass of experimental data available provide a suitable support for the development of computer-based systems (2). The ' 9 N M R spectrum of a compound expresses implicitly the constitution and the configurational stereochemistry of the local environment of each carbon atom therein. The basic strategy for determining a molecular structure from its spectrum consists in inferring these substructural environments and combining them (according to eventual specific constraints) to produce candidate structures. However, the many-to-many relationships between chemical shifts and substructures and the resulting combinative problems make it difficult to automate this procedure.Of the systems currently proposed, two approaches can be distinguished (2). These concern the method by which the 13C NMR spectra are initially interpreted single-resonance subspectrum/substructural interpretation ( Figure 1); multiresonance subspectrum/substructural interpretation ( Figure 2).The best known elucidation strategy is that defied by the DENDRAL project (3). Elucidation here is carried out in three steps: PLAN-GENERATE-TEST. Extension of this approach to 13C NMR (4) is based on single-resonance interpretation. Substructural constraints are deduced during PLAN step and then submitted to the isomer generator GE-NOA (5) at the heart of the system.Other systems also use this strategy, for example CASE (6, 7) which consists of three modules, INTERPRET-ASSEM-BLE-SIMULATE. The combinative problems encountered motivated the development of a new generator (8), more specialized than a modified version of ASSEMBLE (9).In Sasaki's CHEMICS system (IO) the interpretation of various spectroscopic data ('H and 13C NMR, infrared (IR), mass spectrometry (MS)) eliminates, from a set of fundamental fragments, those that are inappropriate. Constraints can be introduced (11) to restrict the number ...

SISTAX: an intelligent tool for recovering information on natural products chemistry

“…The former task has been thoroughly explored by our research group. [4][5][6][7][8][9][10][11][12][13][14][15][16] The latter is only beginning. 17 The system allows the analysis of the The database of SISTEMAT shows all the facilities of an associated database allied to the storage of compound structures in compacted vector forms, which are transformed into connectivity matrices during the search process.…”

“…[1][2][3][4][5][6][7][8][9][10][11] Substructures, allied to other biochemical inferences, are the main tools for chemotaxonomy methodology, and may be useful to discrimimate genera, species etc. 12,13 The aim of this work is to demonstrate how a specialist system developed to assist the chemist in both fields described above can be used for chemotaxonomic purposes.…”

Applications D′Intelligence Artificielle Dans La Chimie Organique. XVII. Nouveaux Programmes Du Projet SISTEMAT

“…Ce programme a ete elabore dans Ie but d'indiquer les grandes SOllS-StruCtures et les squelettes employant un processus tres sophistique it partir du moment ou la confrontation des spectres de RMN au BC est realisee. L'importance de ce programme pour Ie projet SISTEMAT reside dans Ie fait que comme il a ete demontre [16], que Ie manque des SOllSstructures est Ie principal probleme des genentteurs du type DENDRAL [20] ou DARC [21] qui n'evitent pas Ie probleme de l'explosion combinatoire. NollS montrerons par la suite quelques exemples d'application du SISCONST avant de l'utiliser avec Ie generateur en finition.…”

Quantum isomer search

“…In order to generate the isomers, most of these codes, including SKELGEN, CAMGEC, AEGIS, ISOGEN, GI, and MOLGEN [15][16][17][18][19][20] require only the molecular formula as input. Others, such as DENDRAL, GalvaStructures, CONGEN, GENOA , ASSEMBLE 2.0, CHEMICS, EPIOS, GEN, StructEluc, COCON, SpecSolv, ESESOC, SIGNATURE, SENECA, COCOA, SESAMI, CISOC-SES, and X-PERT take as input any combination of molecular formula, spectral information and spectroscopic data, fragments, molecular weight, molar mass, and constraints such as long-range distance constraints [13,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”