Computer Assisted Synthesis Design

The chemical synthesis of carbon-containing molecules has been a very important field of scientific work and endeavor for over a centuiy However, the subject is still far aw ay from being fully developed. One of the major reasons for this is the almost unlimited number of organic structures which can exist as discrete compounds. On the other hand there has been a continuing growth in the ability of chemists to construct increasingly complex molecules. 

How do chemists find a pathway to the synthesis of a new organic compound They try to find suitable starting materials and powerful reactions for the synthesis of the target compound. Thus, synthesis design and chemical reactions are deeply linked, since a chemical reaction is the instrument by which chemists synthesize their compounds synthesis design is a chemist s major strategy to find the most suitable procedure for a synthesis problem. 

The way a synthesis is planned has changed substantially over time. Until the beginning of the 20th century many noteworthy syntheses had been developed, c.g., of alizarin (C. Gracbc, C, Licbermann, 1869) and indigo (A, Bacycr, 1878). 

In the following decades, chemists tried to utilize more and more the knowledge on reactions which had already been gained. A number of landmark syntheses represent the change to modern chemistry, such as the synthesis of the estrogenic steroid equilenin (W. Bachmann, 1939), of pyridoxine (K. Folkers, 1939), and of quinine (R.B. Woodward, W. von E. Doering, 1944) [23]. 

A further advancement in organic synthesis was the accomplishment of multi-step syntheses comprising 20 and more steps and the synthesis of rather unstable organic compounds. It was now feasible to do an experiment on a milligram scale and to separate and identify products from by-products in order to analyze them separately. The application of selective reagents or reaction conditions allowed the synthesis of enantiomerically or diastereomerically pure compounds. 

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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. 

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. 

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. 

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. 

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 ... 

CASD = computer-assisted synthesis design P = product SM = starting material SSM = skeleton of starting material TC = tactical combination. 

A myriad of syntheses have been published since the beginning of organic synthesis with the first preparation of urea by Wbhler in 1828. It is only in 1%7 that a systematic analysis of this activity was attempted in the direction of CASD (computer-assisted synthesis design). To illustrate the diversity of possible approaches to synthesize an organic compound let us consider some typical examples ... 

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