LSD
 Logic for Structure Determination

Introduction

Ready-to-use versions of LSD are available. A specific installation procedure is included.

LSD (download the source version) is free software, distributed under GPL licence.
Here is its user's manual .

Current version is 3.5.3. Last modified: September, 20th 2024.

See the history file.
The history file contains links to older LSD distribtion files.

You will also find here an introductory lecture on structural organic chemistry and an example of LSD use.

CASA is a software for automatic structure verification. It is based on the chemical shift assigment from 1D and 2D NMR data.

PyLSD is a layer over the LSD software. PyLSD deals with problems LSD cannot solve, those in which the atom status is not accurately defined.

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.

Find LSD on linkedin

Find LSD on GitHub

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 13C 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 .sdf (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

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Computer aided spectral assignment in nuclear magnetic resonance spectroscopy.
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J.-M. Nuzillard and G. Massiot.
Logic for Structure Determination.
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A quick method for the automatic detection of anti-Bredt structures.
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Connectivist approach to organic structure determination. LSD-program assisted NMR analysis of the insect antifeedant azadirachtin.
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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.
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Automatic structure elucidation through data dase search and 2D NMR spectra analysis.
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Novel seco-Dibenzopyrrocoline Alkaloid from Cryptocarya oubatchensis.
Organic Letters 2006, 8, 3825-3828. DOI: 10.1021/ol061435f

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).
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Recent advances in the structure elucidation of small organic molecules by the LSD software.
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J.-M. Nuzillard.
Automated Interpretation of NMR Spectra for Small Organic Molecules in Solution.
eMagRes 2014, 3, 287-293. DOI: 10.1002/9780470034590.emrstm1384

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Exploiting the Complementarity between Dereplication and Computer-Assisted Structure Elucidation for the Chemical Profiling of Natural Cosmetic Ingredients: Tephrosia purpurea as a Case Study.
J. Nat. Prod. 2015, 78, 1609-1617. DOI: 10.1021/acs.jnatprod.5b00174

H. I. Januar, N. P. Zamani, D. Soedharma, E. Chasanah.
Logic Structure Determination (LSD) as a Computer-Assisted Structure Elucidation (CASE) for Molecular Structure Determination of Cytotoxic Cembranoids from Soft Coral.
Squalen Bull. of Mar. and Fish. Postharvest and Biotech. 2016, 11, 1-6. DOI: 10.15578/squalen.v11i1.177

J. K. Sihra, M. K. Langat, N. R. Crouch, J.-M. Nuzillard, B. Plainchont, D. A. Mulholland.
Novel triterpenoid derivatives from Eucomis bicolor Bak. (Hyacinthaceae: Hyacinthoideae).
RSC Adv. 2017, 7, 15416-15427. DOI: 10.1039/c6ra28584h

A. Bakiri, B. Plainchont, V. de P. Emerenciano, R. Reynaud, J. Hubert, J.-H. Renault, J.-M. Nuzillard.
Computer-aided Dereplication and Structure Elucidation of Natural Products at the University of Reims.
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J.-M. Nuzillard, B. Plainchont.
Tutorial for the structure elucidation of small molecules by means of the LSD software.
Magn. Res. Chem. 2018, 56, 458-468. DOI: 10.1002/mrc.4612

M. K. Langat, N. B. Crouch, J.-M. Nuzillard, D. A. Mulholland.
Pseudopulchellol: A unique sesquiterpene-monoterpene derived C-25 terpenoid from the leaves of Croton pseudopulchellus Pax (Euphorbiaceae).
Phytochem. Lett. 2018, 23, 38-40. DOI: 10.1016/j.phytol.2017.11.008

M. K. Langat, B. M. Nunda, C. Salter, B. O. Odusina, S. M. Isyaka, E. Mas-Claret, P. A. Onocha, J. O. Midiwo, J.-M. Nuzillard, D. Mulholland.
Diterpenoids from the stem bark of Croton Megacarpoides Friis & Gilbert.
Phytochem. Lett. 2020, 39, 1-7. DOI: 10.1016/j.phytol.2020.07.003

Contributors

Bertrand Plainchont, Ph. D. Student from September 2009 to December 2012 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