Computer LHASA

Early implementations of the CIP rules for computer detection and specification of chirality were described for the LHASA [105], CHIRON [106], and CACTVS [107] software packages. Recently, several commercial molecular editors and visualizers (e.g., CambridgeSoft s ChemOffice, ACD s I-Lab, Accelrys WebLab, and MDL s AutoNom) have also implemented the CIP rules. 

The use of computers for the design of chemical syntheses was first demonstrated by Corey and Wipke in 1969 with their program OCCS [30]. The successor to OCCS, LHASA [31], is generally considered to be the first synthon-based system. Its development is still going on. Currently, three groups are working on LHASA, one at Harvard University, USA [32], one at the University of Leeds, UK [33], and... 

Ott M. A., Noordik J. H. Long-Range Strategies in the LHASA Program The Quinone Diels-Alder Transform J. Chem. Inf. Comput. Sci. 1997 37 98 108 Keywords computer application, quinone Diels-Alder transformations... 

M.A. Ott and J.H. Noordik, Long-range strategies in the LHASA program the Quinone Diels-Alder transform. J. Chem. Inf. Comput. Sci., 37 (1997) 98-108. 

A number of approaches are available or under development to predict metabolism, including expert systems such as MetabolExpert (Compudrug), Meteor (Lhasa), MetaFore [42] and the databases Metabolite (MDL) and Metabolism (Synopsys) [43]. Ultimately such programs may be linked to computer-aided toxicity prediction based on quantitative structure-toxicity relationships and expert systems for toxicity evaluation such as DEREK (Lhasa) (see also Chapter 8) [44]. 

A number of different systems have been developed to conduct computer-aided organic synthesis. Of these, one of the most extensive projects is LHASA ( 3 - 11). The method starts from a target molecule and derives a set of precursor molecules which can be expected to be converted to the target by one synthetic reaction or a simple sequence of reactions. Each precursor molecule so generated serves as the next target and the procedure is repeated, thus generating a tree of synthetic intermediates. Each precursor is somewhat simpler than its parent target molecule. 

Greene N, Judson PN, Langowski JJ, Marchant CA (1999) Knowledge-based expert systems for toxicity and metabolism prediction DEREK, StAR and METEOR. SAR QSAR Environ Res 10 299-314 Greene N (2002) Computer systems for the prediction of toxicity an update. Adv Drug Deliv Rev 54 417—431 Lhasa homepage http //www.chem.leeds.ac.uk/luk/... 

The computer-assisted synthetic analysis designated OCSS (organic chemical simulation of synthesis) and LHASA (logic and heuristics applied to synthetic analysis) were designed to assist chemists in synthetic analysis by Corey et LHASA generates trees of synthetic intermediates from a target molecule by analysis in the retrosynthetic direction. 

The computational toxicology software programs and models were obtained by FDA/CDER/ICSAS through cooperative research and development agreements with MDL Information Systems and Lhasa Ltd (Benz, 2007)... 

Retrosynthetic Analysis. An approach to computer-assisted synthesis design that starts with the products of a reaction or sequence of reactions and works backwards toward the reactants. An example program that implements retrosynthetic analysis is the LHASA program of E. J. Corey s group. 

Corey and Feiner have developed a computer program (LHASA) for conformational analysis and for determining the destabilization energies (Ep) in substituted cyclohexane derivatives. In the following discussion, we will adopt their A, G and U designations and use the corresponding values for evaluating steric interactions. 

DEREK for Windows is a computer-based application that uses a knowledge base approach to predict toxic hazards (including carcinogenicity) of chemicals. It is developed by Lhasa Limited (http //www.lhasalimited.org/index.php cat=221 owner=220 sub cat=221), with SAR contribution from members. The cancer module contains alerts describing structural features associated with carcinogenicity. Each alert is supported by comment, references, and examples describing the evidence on which it has been based. 

This information is then used to disconnect bonds in the target, simplifying the structure along reasonable chemical reaction pathways. Wipke and Howe- defined the important bonds that are disconnected (as approached by the computer program LHASA, sec. 10.4.B, developed by Corey for analysis of retrosynthetic pathways). 

These concepts were developed into the computer program SYNGEN147 (SYNthesis GENeration). As with Corey s LHASA program, inspection of the main principles of the program can offer useful information for a synthesis. It is emphasized that this section has only touched the surface of Hendrickson s detailed and comprehensive analysis. Once understood, any target can be analyzed in detail to provide a synthetic tree. 

Research into the use of digital computers to assist in the derivation of synthetic routes to complex molecules has been in progress for several years at Havard. The program is called LHASA Logic and Heuristics Applied to Synthetic Analysis). The research is being carried out by a team headed by Corey. l... 

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