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.