Synthesis Computer Assisted

After approaches to the solution of the major tasks in chemoinformatics have thus been outlined, these methods are put to work in specific applications. Some of these apphcations, such as structure elucidation on the basis of spectral information, reaction prediction, computer-assisted synthesis design or drug design, are presented in Chapter 10. 

In 1967, work was presented from a Sheffield group on indexing chemical reactions for database budding. In 1969, a Harvard group presented its first steps in the development of a system for computer-assisted synthesis design. Soon afterwards, groups at Brandeis University and TU Munich, Germany, presented their work in this area. 

Program systems for computer-assisted organic synthesis (CAOS) have been under development since the early 1970s [27]. The program systems for computer-assisted synthesis planning can be subdivided into two groups information-oriented and logic-oriented systems [28]. 

We have already emphasized our view that the evaluation of chemical reactions and synthetic pathways is of preeminent importance in any system for computer-assisted synthesis design or reaction prediction. The quality of the evaluation process will determine to a large extent the overall quality of such a system. 

The second stage of this approach is the evaluation of the reaction. This step is the most crucial one in our program, as well as in all other programs of computer-assisted synthesis (16a-16d). The evaluation by the computer is optional. If it is not desirable, the computer proceeds to the generation of all formal possibilities, otherwise the control passes to the EVALUATION module, which discards some solutions. The evaluation is based on the perception of various features of the catalyst and on some rules that we have introduced. These rules concern the two classes of two-electron reactions which will be presented in Section III. The first one contains key reactions of... 

Ugi I, Bauer J, Bley K, Dengler A, Fontain E, Knauer M, Lohberger S, (1991) Computer-assisted synthesis design, a status report, J Mol Structure (Theochem), 230 73... 

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. 

Computer-assisted synthesis and reaction planning in combinatorial chemistry. Perspectives in Drug Discovery and Design, 20, 245-264. 

In the decade since the first published description of a computer program capable of deriving synthetic routes to complex molecules, ) the field has grown into a lively discipline. GLaiLiA) Nevertheless, it cannot yet be said that computer assisted synthesis is an accepted research tool for many practicing synthetic chemists. 

While Merck has for a long time recognized the computer s potential in this area, CD the decade was half over before the field was sufficiently advanced for an in-house effort to be considered. When a computer assisted synthesis project was begun, a number of major design decisions were quickly made. 

Gasteiger, J., et al., Computer-Assisted Synthesis and Reaction Planning in Combinatorial Chemistry, Persp. Drug Discov. Design, 20, 1, 2000. 

Pfortner, M. and Sitzmann, M., Computer-Assisted Synthesis Design by WODCA (CASD), in Handbook of Chemoinformatics — From Data to Knowledge in 4 Volumes, vol. 4, Gasteiger, J., Ed., Wiley-VCH, Weinheim, 2003, 1457. 

Computer Assisted Synthesis Planning (CASP) Can predict precursor s need for synthesis as well as most likely metabolites... 

POSTER SESSION COMPUTER ASSISTED SYNTHESIS DESIGN USING CHIRON AND REACCS... 

Despite the fact that both our efforts and those of computer-assisted synthesis design involve executing a representation of a chemical reaction in the computer, there are fundamental philosophical and methodological differences, as summarized in Fig 2 and detailed as follows ... 

Figure 2. Contrasts between the methods and goals of development of a synthesis tree in computer-assisted synthesis and development of a reaction sequence tree in structure elucidation. We denote two applications of reaction sequences A) conversion of known precursors into unknown compounds, a problem encountered in mechanistic studies B) conversion of candidate structures for an unknown into a series of products, usually employed in the general problem of structure elucidation.

A) An Example of Application of Reaction Sequences to Mechanistic Problems There are at least two ways to apply the reaction sequence capabilities of CONGEN to mechanistic problems Some of the procedures discussed subsequently can be carried out with current computer-assisted synthesis programs whenever a single compound represents the starting point ... 

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. 

WHAT CAN GO WRONG WITH COMPUTER-ASSISTED SYNTHESIS SOFTWARE... 

Zefirov, N.S. Gordeeva, E.V. Computer-assisted Synthesis . Russ. Chem. Rev. 1987,56, 1002-1014 and references within. 

A complete journal issue including eleven articles is dedicated to computer assisted synthesis Rec. Trav. Chim. 1992, 111, 239-334. 

A computer-assisted process for solving problems. Setting out from a target, a path to potential starting points is searched in a backward direction. This method is used for computer-assisted synthesis planning to find suitable synthesis precursors or available starting materials. 

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