Synthesis Plan Database

The International Union of Pure and Applied Chemistry (IUPAC, 10) proposed a definition of computational chemistry about 15 years after the term was already well established in the lexicon of chemists A discipline using mathematical methods for the calculation of molecular properties or for the simulation of molecular behavior. It also includes, e.g., synthesis planning, database searching, combinatorial library manipulation. The open-ended second part of this statement reflects the disparate opinions of the IUPAC committee and others who contributed comments. 

Expert Systems and Smart Databases as Aids to Organic Synthesis Planning. ... 

The Knowledge base-Oriented System for Synthesis Planning (KOSP) was developed by Satoh and Funatsu and uses reaction databases for the retrosynthe-sis approach [115]. KOSP provides strategic site-pattern perception and precursor skeleton generation and evaluates retrosynthetic schemes. This system is based on knowledge bases in which reactions are abstracted by structural or stereo characteristics of reaction sites and their environments. 

It would also be interesting to work on the automatic creation of a synthesis planning knowledge base using the factual information from a reaction database. 

Interfacing between reaction retrieval and synthesis planning has so far been used for exchange of database information. But why go fiirther into an integrated system capable of query formulation and query translation ... 

Figure 6.27 shows the analysis for a heterocyclic compound highlighted in a paper on electronic reaction databases and synthesis network searches [52]. The proposed synthesis plan is shown in Figure 6.28 that features two branches that converge in a three-component coupling reaction. 

Of the 1050+ plans examined in this database, the poorest performing ones refer to the synthesis of colchicine. Seven out of nine published plans to date for this target compound fall into the same trap of the isocolchicine—colchicines equilibrium in the late stages of the synthesis plans as shown in Figure 11.35. The Cha and the Banwell plans are the exceptions. The final structure... 

This chapter presents several plots of correlations between key metrics parameters for the 1050 plans docnmented in the extensive synthesis database. Each trend is discnssed in the context of achieving optimum and green syntheses. Examples of synthesis plans that achieve some measure of greenness are highlighted. The reader is referred to Chapters 5 and 6 regarding the definitions of metrics parameters. 

FIGURE 13.2 An example for a BICEPS planning database that is used to collect and characterize synthesis ideas (virtual compounds) for a research project. A number of molecular properties are predicted and used to prioritize synthesis ideas. BICEPS planning databases are a special type of project data mart. 

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,... 

The use of independent blocks in SMD format allows a program to skip over blocks which it does not require, or is unable to process. This should faciUtate exchange of structures between tot y different programs, such as systems for chemical structure database management, molecular modelling, chemical synthesis planning, QSAR and spectroscopy-based structure elucidation. 

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. 

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