Reaction-database systems

To deal with the flood of information— chemical, biological, and clinical—it became essential over the years to develop chemical information computing systems (i.e., chemical and reaction database systems) from which the chemist and biologist could obtain up-to-... 

Other relational structure/reaction database systems are available commercially. These include the Thor system from Daylight... 

This account of the LHASA and CAMEO programs has been necessarily very limited readers interested in further details should contact the suppliers of the software as listed in the Software appendix. Another approach to the problem of synthesis planning is to provide literature references to model reactions, thus allowing the chemist user to make his or her own assessment of feasibility, using his or her own expert system A number of reaction database systems are in common use (e.g., REACCS,... 

In this paper we describe how the ORAC reaction database system has been integrated with the LHASA synthesis planning program. This interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved from ORAC and displayed to the user. The problem of sequence searching in reaction database systems is also explored and approaches to this problem are described. Finally, the potential use of synthesis planning systems to identify and classify links between reactions in ORAC for use during sequence searching is considered. 

Reaction schemes for making specific compounds from readily available starting materials or solving particular sjmthetic problems are commonly reported in the literature. It is therefore desirable that a reaction database system allow input and indexing of complete reaction schemes. A reaction database system should be able to search reaction schemes for sequences of reactions that satisfy a query. In addition, the search program should be able to link together individual reactions in a database to find sequences implicitly represented in a reaction database by identif3dng if the product of one reaction is the reactant of another. 

Figure 1 summarises the S3mergic relationship between synthesis planning and reaction database systems that is explored in this paper. 

The primary purpose of a reaction database system is to provide quick and easy access to the reaction literature. Users of synthesis planning programs have a need for such access to the literature in elaborating routes suggested by an analysis. An interface between LHASA and ORAC has recently been developed to provide such a link. The interface allows literature precedents for synthetic steps proposed by LHASA to be retrieved automatically from ORAC s database of over 120,000 reactions and to be displayed to the user on an ORAC Display Form. Company databases can also be accessed to search and display in-house preparative methods and processes in conjunction with databases supplied by ORAC Ltd. 

An explicit reaction scheme is one that has been reported in the literature. Explicit schemes may or may not be indexed in a special way in the reaction database system. Approximately 15% of the reactions in Theilheimer s Synthetic Methods are reported as reaction schemes. In the ORAC Theilheimer database, each individual reaction step and the overall transformation is stored as a separate entry. For example, a sequence A—>C— D is indexed as the three reactions A->B, B->C and C D, plus the overall transformation A- D. A drawback of this approach is that transformations such as B D cannot be located in answering a... 

Reaction database systems need to be able to store reaction schemes and search for reaction sequences involving both explicit schemes and implicit links between individual reactions in a database. A third class of links between reactions has been defined which involves identifying the presence of the reacting environment of one reaction in the product of another synthesis design programs could prove useful in classif3dng and indexing such linl. ... 

Although all reaction database systems come with their native structure editor for query input, most of them permit input of structures or reactions produced by standard chemical drawing programs, linear notations (SMILES), or standard structure file formats. 

Sf The Chemlnjbrm RX reaction database is produced by FIZ Chemie, Berlin, Germany, and marketed by MDL Information Systems, Inc., San Leandro, CA, USA. 

The Chemical Abstracts System (CAS) produces a set of various databases ranging from bibliographic to chemical structure and reaction databases. All the databases originate from the printed media of Chemical Abstracts, which was first published in 1907 and is divided into different topics. Author index, general index, chemical structure index, formula index, and index guide arc entries to the corresponding database (Table 5-3). 

Reactions can be considered as composite systems containing reactant and product molecules, as well as reaction sites. The similarity of chemical structures is defined by generalized reaction types and by gross structural features. The similarity of reactions can be defined by physicochemical parameters of the atoms and bonds at the reaction site. These definitions provide criteria for searching reaction databases [23],... 

To be able to define reaction planning, reaction prediction, and synthesis design To know how to acquire knowledge from reaction databases To understand reaction simulation systems... 

In spite of the importance of reaction prediction, only a few systems have been developed to tackle this problem, largely due to its complexity it demands a huge amount of work before a system is obtained that can make predictions of sufficient quality to be useful to a chemist. The most difficult task in the development of a system for the simulation of chemical reactions is the prediction of the course of chemical reactions. This can be achieved by using knowledge automatically extracted from reaction databases (see Section 10.3.1.2). Alternatively, explicit models of chemical reactivity will have to be included in a reaction simulation system. The modeling of chemical reactivity is a very complex task because so many factors can influence the course of a reaction (see Section 3.4). 

More elaborate scheme.s can he envisaged. Thus, a. self-organizing neural network as obtained by the classification of a set of chemical reactions as outlined in Section 3,5 can be interfaced with the EROS system to select the reaction that acmaliy occurs from among various reaction alternatives. In this way, knowledge extracted from rcaetion databases can be interfaced with a reaction prediction system,... 

The reaction database compiled on Biochemical Pathways can be accessed on the web and can be investigated with the retrieval system C ROL (Compound Access and Retrieval On Line) [211 that provides a variety of powerful search techniques. The Biochemical Pathways database is split into a database of chemical structures and a database of chemical reactions that can be searched independently but which have been provided with efficient crosslinks between these two databases. 

One of the hits found in the Chem Inform reaction database is shown in the window for reaction substructure searches in Figure 10.3-55. It fits the synthesis problem perfectly, since in the synthesis direction it forms the coumarin ring system directly, in one step. 

MDL Information Systems, Inc. MDL provides modular software systems for managing chemical information, as weU as related molecular and reaction databases for use with the software. MDL s database management programs, MACCS-II and REACCS, provide access to compound and reaction databases and also have the capabiHty to manage user-created databases (37). Although MDL is not considered to be an on-line database vendor, it is mentioned here because of the value of its information products and services to the chemical industry. 

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