LSD
Logic for Structure Determination

LSD is free software, distributed under GPL licence.

Here is its user's manual
and installation instructions for MS-DOS (Windows) .

See the history file.

Please send your questions, remarks and suggestions to: jm.nuzillard@univ-reims.fr
You may also let me know if you want to be informed (or not) about new releases.
More free chemistry software is available on the linux4chemistry website.

Description

The aim of the LSD program is to find all possible molecular structures of an organic compound that are compatible with its spectroscopic data.

Structure building relies on connectivity data found in 2D NMR spectra, without any reference to a chemical shift database. Molecular structures containing up to 50 non-hydrogen atoms were investigated by means of the LSD program.

The measurement protocol that is required by LSD includes the recording of 1D 1H and 13C as well as 2D COSY, HSQC and HMBC spectra. The status of each atom must be defined. It includes the atom symbol, the hybridization state (sp3, sp2 or sp), the number of attached hydrogen atoms, and the electric charge. This part of the data set is most often easily deduced by the user from elementary chemical shift knowledge. The status of the heteroatoms is deduced from the elemental molecular formula.

Carbon-carbon bonds are deduced from COSY and HSQC data while HMBC and HSQC data provide connectivity relationships through one or two bonds for non-hydrogen atom. The constraints imposed by atom status and 2D NMR data may be enforced by other atom neighborhood relationships. For example, it is possible to force a carbon atom to be bound only to carbon atoms. The user is responsible for such supplementary data. Contradictory constraints lead LSD to fail in the search of a solution structure.

The low resolution of HMBC and HSQC spectra in the C-13 chemical shift domain causes peak assignment ambiguities. It is possible to define groups of resonances and to assign a HMBC correlation peak to a group. This means that the correlation is caused by at least one member of the group.

The solutions may be selected using a substructure or a combination of substructures. Those violating Bredt's rule are also discarded.

The input to LSD is coded by the user as a text file, according to the instructions in the MANUAL_ENG.html document.

A program named OUTLSD reads the generated solutions and converts them into various formats: bonds lists, 2D coordinates, fancy 3D coordinates (fancy, due to the lack of stereochemical information), and SMILES chains. The 2D coordinates can be converted to Postscript drawings and to .mol (SDF) files.

Execution of the LSD program may be controlled by specific instructions for output formatting such as: single step execution, search of the biggest found fragment (for debugging purpose), report writing, verbosity level, substructure search.

Tens of structures were investigated by means of the LSD program, essentially in the field of natural product chemistry, and especially for terpenes and alkaloids.

Bibliography

J.-M. Nuzillard and G. Massiot.
Computer aided spectral assignment in nuclear magnetic resonance spectroscopy.
Analytica Chimica Acta 1991, 242, 37-41.

J.-M. Nuzillard and G. Massiot.
Logic for Structure Determination.
Tetrahedron 1991, 47, 3655-3664.

J.-M. Nuzillard.
A quick method for the automatic detection of anti-Bredt structures.
J. Chem. Inf. Comput. Sci., 1994, 34, 723-724.

S. V. Ley, K. Doherty, G. Massiot and J.-M. Nuzillard.
Connectivist approach to organic structure determination. LSD-program assisted NMR analysis of the insect antifeedant azadirachtin.
Tetrahedron 1994, 50, 12267-12280.

J.-M. Nuzillard, W. Naanaa, and S. Pimont.
Applying the constraint satisfaction paradigm for structure generation.
J. Chem. Inf. Comput. Sci., 1995, 35, 1068-1073.

G. Almanza, L. Balderama, C. Labbé, C. Lavaud, G. Massiot, J.-M. Nuzillard, J. D. Connolly, L. J. Farrugia, and D. S. Rycroft.
Clerodane diterpenoids and ursane triterpenoid from Salvia haenkei.
Computer-assisted structural elucidation.
Tetrahedron, 1997, 53, 14719-14728.

J.-M. Nuzillard.
Détermination assistée par ordinateur de la structure des molécules organiques.
J. Chim. Phys. 1998, 95, 169-177.

G. Massiot, C. Lavaud, and J.-M. Nuzillard.
Structure elucidation of plant secondary products. Chemical from plants. Perspectives on plant secondary products.
Imperial College Press, 1999, pp. 187-214.

J.-M. Nuzillard, J. D. Connolly, C. Delaude, B. Richard, M. Zèches-Hanrot, and L. Le Men-Olivier.
Computer-assisted structural elucidation. Alkaloids with a novel diaza-adamantane skeleton from the seeds of Acosnium panamense (Fabaceae).
Tetrahedron 1999, 55, 11511-11518.

D. Mulholland, M. Randrianarivelojosia, C. Lavaud, J.-M. Nuzillard, and S. L. Schwikkard.
Limonoid derivatives from Astrotrichilia voamatata.
Phytochemistry 2000, 53, 115-118.

D. Mulholland, S. L. Schwikkard, P. Sandor, and J.-M. Nuzillard.
Delevoyin C, a tetranortriterpenoid from Entendophragma delevoyi.
Phytochemistry 2000, 53, 465-468.

J.-M. Nuzillard.
Automatic structure determination of organic molecules: principle and implementation of the LSD program.
Chinese Journal of Chemistry 2003, 21, 1263-1267.

D. A. Mulholland, A. Langlois, M. Randrianarivelojosia, E. Derat, J.-M. Nuzillard.
The structure elucidation of a novel derivative from Tachiadenus longiflorus (Gentianaceae) using the LSD programme and quantum chemical computations.
Phytochemical analysis 2006, 17, 87-90.

J.-M. Nuzillard, V. P. Emerenciano.
Automatic structure elucidation through data dase search and 2D NMR spectra analysis.
Natural Product Communications 2006, 1, 57-64.

A. Toribio, A. Bonfils, E. Delannay, E. Prost, D. Harakat, E. Hénon, B. Richard, M. Litaudon, J.-M. Nuzillard, J.-H. Renault.
Novel seco-Dibenzopyrrocoline Alkaloid from Cryptocarya oubatchensis.
Organic Letters 2006, 8, 3825-3828.

D. A. Mulholland, M. K. Langat, N. R. Crouch, H. M. Coley, E. M. Mutambi, J.-M. Nuzillard.
Cembranolides from the stem bark of the southern African medicinal plant, Croton gratissimus (Euphorbiaceae).
Phytochemistry 2010, 71, 1381-1386.

B. Plainchont, J.-M. Nuzillard, G. V. Rodrigues, M. J. P. Ferreira, M. T. Scotti, V. P. Emerenciano.
New improvements in automatic structure elucidation using the LSD (Logic for Structure Determination) and the SISTEMAT expert systems.
Natural Product Communications 2010, 5, 763-770.

LSD, as seen by ACD.

Contributors

Bertrand Plainchont, Ph. D. Student since September 2009 at the Institute for Molecular Chemistry of Reims, France.

Pr. Vicente de Paulo Emerenciano, Chemistry Institute, University of São Paulo, for giving us access to the SISTEMAT database from which the collection of natural product skeletons was extracted.

Etienne Derat, UMR 7611 CNRS "Organic synthesis chemistry",
University Pierre et Marie Curie Paris VI, France,
for the creation of the first MacOS X binary files.

back to the main page of the author's lab

Copyright(C)2000 CNRS-UMR 7312-Jean-Marc Nuzillard