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In combinatorial chemistry, hundreds of thousands of reactions are
run in parallel, on beads, or simultaneously in solution. A careful planning
of these reactions is therefore of paramount importance in order to influence
the products obtained in these experiments.
If the synthesis
of an individual organic compound or a combinatorial library is planned
the most important questions for an organic chemist are:
- Which suitable
starting materials are (commercially) available for the synthesis of the
target compound?
- What is the
most convenient and efficient synthesis towards the target compound?
- Which structural
manifoldness of my starting materials is available if
a the synthesis of combinatorial library is planned
?
- Are there any
suitable and powerful synthesis reactions?
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The program system WODCA (Workbench for the Organization of Data for
Chemical Applications) has been developed to assist in the planning of
the synthesis of individual target compounds. Work of recent years now
also enables its use in designing entire libraries of compounds.
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To search for available starting materials, similarity searches, substructure
searches, and some classical retrieval methods such as full structure search,
name search, empirical formula search, etc. have been integrated into the
system. All searches can be applied to a number of catalogs of available
fine chemicals (e.g. Fluka). In addition, compound libraries such as in-house
catalogs can easily be integrated.
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Only in simple synthesis problems one can expect that a search for suitable
starting materials already succeeds with the target compound. In most cases,
the synthesis problem has to be simplified by first generating synthesis
precursors. Therefore, methods for the search and evaluation of strategic
bonds have been implemented in WODCA.
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In order to make WODCA more capable for use in designing the synthesis
of libraries of compounds, substructure search methods have been included
in the system. These, in conjunction with the search for strategic bonds
can provide a series of representatives of certain classes of compounds
that can act as precursors for the synthesis of an entire library.
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In order to verify a retrosynthetic step suggested by WODCA a direct
connection to reaction databases (e.g. Theilheimer, ChemInform) has been
established in the most recent version of WODCA. Reaction databases are
containing a wealth of reactions performed in the laboratory and published
in the literature.
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Gasteiger, J.; Engel, T.; Editors "Chemoinformatics - a Textbook"
Wiley-VCH, Weinheim 2003.
Gasteiger, J.; Editor "Handbook of Chemoinformatics"
Wiley-VCH, Weinheim 2003.
Gasteiger, J.; Pförtner, M.; Sitzmann, M.; Höllering, R.; Sacher,
O.; Kostka, T.; Karg, N. "Computer-assisted synthesis and reaction planning
in combinatorial chemistry" Perspectives in Drug Discovery and Design
2000, 20, 245-264.
Ihlenfeldt, W. D.;
Gasteiger, J. "Computer-assisted planning of organic syntheses: the second
generation of programs" Angewandte Chemie, International Edition in English
1996, 34, 2613-2633.
Ihlenfeldt, W. D.; Gasteiger, J. "Computergestützte Planung organisch-chemischer
Synthesen: Die zweite Programmgeneration" Angewandte Chemie 1995
, 107, 2807-2829.
Gasteiger, J.; Ihlenfeldt,
W. D.; Fick, R.; Rose, J. R. "Similarity concepts for the planning of organic
reactions and syntheses" Journal of Chemical Information and Computer Sciences
1992, 32, 700-712.
Fick, R.; Ihlenfeldt,
W. D.; Gasteiger, J. "Computer-assisted design of synthesis for heterocyclic
compounds" Heterocycles 1995, 40, 993-1007.
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Markus Sitzmann 2003
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