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    Copyright(C)2000 CNRS-Laboratoire de Pharmacognosie-UMR 6013-Jean-Marc Nuzillard

    LSD is free software; you can redistribute it and/or modify
    it under the terms of the GNU General Public License as published by
    the Free Software Foundation; either version 2 of the License, or
    (at your option) any later version.

    LSD is distributed in the hope that it will be useful,
    but WITHOUT ANY WARRANTY; without even the implied warranty of
    MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
    GNU General Public License for more details.

    You should have received a copy of the GNU General Public License
    along with LSD; if not, write to the Free Software
    Foundation, Inc., 59 Temple Place, Suite 330, Boston, MA  02111-1307  USA


1. Installation

See the INSTALL_ENG.txt (in English) or the INSTALL_FR.txt (en français) file.


2. Running LSD

See the MANUAL_ENG.html (in English) or the MANUAL_FR.txt (en français) file.


3. Author

Jean-Marc Nuzillard
Pharmacognosy lab
University of Reims
France
http://www.univ-reims.fr/Labos/UPRESA6013

Please send your comments to jm.nuzillard@univ-reims.fr


4. Overview of the LSD program

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 or sp2)
and the number of attached hydrogen atoms.
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.
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 
(in English) or in the MANUAL_FR.html (in French) 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) for Macromodel,
SMILES chains and .mol data used by some commercial software.

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.

Dozens of structures were investigated by means of
the LSD program, essentially in the field of
natural product chemistry, and especially for
terpenes and alkaloids.
This work led to scientific publications:

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.
Determination assistee par ordinateur de la
structure des molecules 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. Zeches-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.


5. Files

The LSD-3.0.2 directory contains the following files and directories

Cygwin/		Cygwin specials
Data/ 		a directory with LSD data sets
GenposSrc/ 	Source code for the conversion of 2D coordinate files to Postscript
HISTORY 	a short history of the LSD program
INSTALL_ENG.txt	installation instructions, in English
INSTALL_FR.txt	installation instructions, in French
Irix/		IRIX specials
LICENSE 	the text of the GNU Public Licence
Linux/		Linux specials
LsdSrc/		source code for LSD
MANUAL_ENG.html the LSD manual, in English
MANUAL_FR.html 	the LSD manual, in French
OutlsdSrc/ 	source code for OUTLSD, a structure drawing utility
README	 	this file
TODO 		a very uncomplete list of things to do
dialog.tcl 	a Tcl/Tk script for dialog widgets
install.sh	the installation shell (sh) script
m_edit.tcl	a Tcl/Tk script for 2D structures editing

Each system specific directory (Cygwin/ Irix/ Linux/ Darwin/) contains
the following files:

chklsd	 	a script for quick LSD data checking
m_edit	 	a wrapper for m_edit.tcl
makefile 		compilation and installation script
solve 		a wrapper script for lsd, outlsd and genpos.

The Darwin folder also contain compiled binaries:

lsd			lsd itself
outlsd		the drawing generator
genpos		the postscript generator

6. Credits

I thank Etienne Derat, from UMR CNRS 6519, 
"Réactions sélectives et Applications" lab, University of Reims, France
for the building and testing of Darwin binaries.

Modified: Thu Jul 11 21:42:38 2002 GMT
Page accessed 10067 times since Thu Jul 11 23:05:45 2002 GMT