Transform Substructures Searching

Figure 4. ChemBase Transformation Substructure Search Query...

Molecular descriptors play a fundamental role in chemistry, pharmaceutical sciences, environmental protection policy, health research, and quahty control, being the way molecules, thought of as real bodies, are transformed into numbers, allowing some mathematical treatment of the chemical information contained in the molecule. Therefore molecular descriptors allow us to find - structure/response correlations and perform - similarity searching, - substructure searching, etc. 

With Comprehensive Asymmetric Catalysis we hope to fill this gap. Comprehensive means that all important classes of enantioselective catalytic transformations are covered but it does not imply an extensive lexicographic compilation of examples. The aim was a concise and readable overview of the field, providing a clear picture of the state of the art. The reader should be able to recognize the scope and limitations of a specific catalyst or method and find the pertinent references for a more detailed bibliographic study. The electronic version with reaction and substructure search options should be particularly useful for this purpose. 

There are several interesting applications which can be developed with the HView of Figure 10. For example, one can determine what reactions are available, at high 5deld, to synthesise molecules located in a corporate database by identity or substructure search. Or, one can identify novel transformations of a given molecule in the corporate database, quahfied by the amount available in the sample inventory. 

Smaller companies tend to have fewer concerns around, for example, system scalability, global WAN performance, and complex systems integration. They are rather more driven by the pure functionality of the ELN that is addressing the specific scientific disciplines of interest. Key drivers in this sector of the market have been medicinal chemistry departments, where the obvious benefits of searching existing reactions by substructure and reaction transformations, the ability to automate stoichiometry calculations, the ability to load spectral information, etc. have made for easy adoption and clear and realizable benefits. 

SEARCH lor the substructures required to perform a given transformation, which corresponds to a possible reaction, is then performed by the program (Section II,C). 

The actual search for a particular transform is accomplished by looking for a characteristic substructure, evaluating that substructure, and providing reactions to build it as a precursor. A major drawback to the program is the lack of attention to stereochemistry in the target or disconnect products. In one example... 

The next step is to find all reactions in the other ORAC databases that correspond to a CASP synthesis proposal or to a CASP transform in general. For this purpose CASP can deliver the reactant and product substructures with corresponding differences and put them into a query file for ORAC to search. The detected cross references can be stored in the CASP transform library for quick retrieval. Doing this manually so far for our ongoing transform work we found that many transforms have no corresponding ORAC (or SYNLIB) reactions. It seems that some classical chemistry is not yet represented therein. 

The criterion of applicability would require that the target structure contain the -C(OH)-C-CO-substructure and would not be applicable in the State Space search. In search conducted in the Planning Space, if the transform indicated is considered relevant to the target structure (e.g., if the presence of the alcohol and an unsubstituted 1,4 carbon is sufficient) then this transform may be used. The original synthesis problem is replaced with two subproblems shown in Scheme II. 

Operation of the System Each of the substructural modification patterns in the database is utilized as the "rule in the system. The structure of a primary lead compound represented by Ri-(ai) is first introduced in the system. Then, the search of the database is initiated. If an example, in which a structure Si-(ai) is successfully transformed to an elaborated structure Si-(bi), is hit by the search, then, the system "automatically" constructs a candidate structure Ri-(bi) for the higher-ordered lead compound. The substructural modification pattern from ai to bi originally identified in the structural evolution example from Structure A, [Si-(ai)], to Structure B, [Si-(bi)], is... 

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