Reaction database systems, ORAC

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. 

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... 

On the other hand, the data in the base file may be converted into an SMD file (Standardised Molecular Data) which is used by the companies of the CASP pool in Europe for interchanging substance and reaction data. Interfaces to commercially available reaction retrieval systems, using the SMD data structure, exist or are being developed. In this way, in-house versions of the database to be used with REACCS, ORAC, SYNLIB, etc., will be made available. 

Similarity searching in reaction databases has gained widespread interest since it became available (in REACCS and ORAC) about two years ago. The definition of similarity of reactions in these reaction retrieval systems is based on common substructural features in the reaction centres and in the reactants. Without doubt, these definitions of reaction similarity are of great usefulness. However, we wanted to broaden the discussion of reaction similarity and search for additional helpful ideas. To achieve this we took a totally different approach to specify the similarity of reactions. Our approach is based on the idea that chemists often want to know the exact conditions for running a reaction. We assumed that similar reactions should be those that proceed under similar reaction conditions. 

FIZ Chemie = Fachinformation.szentrum Cheniie ISl = institute for Scientific Information IRDAS = ISIS reaction database access system ISIS = integrated scientific information system JSM = Journal of Synthetic Methods MACCS = molecule access system MOS = Metlwd.s in Organic Synthesis, ORAC = Organic Reaction Acce.ss by Computer REACCS = Reaction Access System SMD = standard molecular data SPORE = Solid Phase Organic Reactions, STN = Scientific and Technical Information Network SYNLIB = Synthesis Library. 

ORAC was developed by A. P. Johnson et al., at Leeds University, and was later produced by ORAC Ltd. Since the takeover by MDL, ORAC has no longer been upgraded, but its core database (about 65000 reactions, coverage mainly since 1980, but with a significant number of earlier reactions) survives as part of MDL s RefLib (.see Section 3.2.3). ORAC had a few outstanding features that appeared only later in other reaction-retrieval systems, or are still missing in them thesaurus-based reaction classification (see Section 4.11), both bonds or atoms definable as reaction centers, both explicit... 

This is a combined archival database with 171629 reactions originating predominantly from about 300 Journals and some patents. It comprises the Theilheimer databa.se (46785 reactions 1946-1980), the core database from the former ORAC system (about 65 000 reactions, mainly 1980-1991), and several databases produced by MDL (CLF Current Literature File 36600 general synthetic reactions 1983-1991. CHIRAS 13 200 asymmetric reactions 1975-1991. Metalysis 12000 metal-mediated reactions 1974-1991). Although the time coverage of RefLib does really start at 1946, the onset of Theilheimer, there are almost 4000 reactions with pre-1946 references (2600 with literature only before that year). 

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