Computer programs LHASA

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. 

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. 

One important aspect of the project has been the writing of a general purpose computer program which will aid the laboratory chemist and will employ both the basic and more complex techniques for synthetic design as elucidated by this study. The program (hereafter also called LHASA) is intended to propose a variety of synthetic routes to whatever molecule it is given. The responsibility for final evaluation of the merit of the routes lies with the chemist. The program is to be an adjunct to the laboratory chemist as much as any analytical tool. 

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]. 

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. 

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... 

It is precisely this failure to consider all possible routes that makes a program like LHASA both useful and necessary. Computers are well known for their ability to perform rote tasks a great number of times without complaint. Examination of potential synthetic pathways may be broken down into sufficiently small steps as to be amenable to computer implementation. 

Currently the most powerful program for computer-assisted synthesis is probably LHASA (Logic and Heuristics Applied to Chemical Synthesis), which has evolved from work begun at Harvard university in the late 1960s by Corey and Wipke for more information, contact the LHASA Group at Harvard. 

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