Development of a Computer-Aided Organic Synthesis Design System CASINO

We have developed a new organic synthesis design system named CASINO (Computer-Aided Synthesis Inference for Organic Compounds), which is a comprehensive program package with various functions. Empirically oriented and logically oriented synthetic route planning have been realized in various computer-aided design systems. Thinking process in synthetic route planning is systematically simulated in empirically oriented approach. Meanwhile, mathematical combinations of bond exchange patterns are generated in logically oriented approach. Both aspects of computer-aided synthesis design have been combined in CASINO. We describe three main modules in CASINO: the module for (i) generation of reaction sequences, (ii) chiral synthon recognition, and (iii) retrosynthetic analysis. In addition, examples of applications of CASINO to several synthetic problems are presented. Chemical structures and chemical reactions are numerically manipulated in CASINO. The algebraic model using matrix representation, i.e. the bond-electron and reaction matrices, is adopted. Synthetic reactions and available compounds are written in the databases using matrix representations. CASINO generates various reaction sequences connecting a starting compound and a target molecule, which are specified by the user. CASINO will cover all the possibilities of combinations of bond exchange patterns in the database. Chiral synthon recognition is based on agreement of structural features and stereochemistry of a given target molecule with those of available compounds in the database. The set reduction method and the modified stereochemical extension of Morgan algorithm (SEMA) are used in this module. For retrosynthetic analysis, we classified synthetic reactions into several patterns on the basis of electron movement and bond exchange accompanying the reactions. We extracted generic retrosynthetic patterns corresponding to various C-C bond forming reactions and functional interconversion methods. Heteroatoms are considered either electropositive (M) or electronegative substituents. CASINO generates synthetic precursors by applying generic retrosynthetic patterns to a target molecule.