Enumeration of Ring鈥揅hain Tautomers Based on SMIRKS Rules

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• 作者：Laura Guasch ; Markus Sitzmann ; Marc C. Nicklaus
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2014
• 出版时间：September 22, 2014
• 年：2014
• 卷：54
• 期：9
• 页码：2423-2432
• 全文大小：488K
• ISSN：1549-960X

文摘

A compound exhibits (prototropic) tautomerism if it can be represented by two or more structures that are related by a formal intramolecular movement of a hydrogen atom from one heavy atom position to another. When the movement of the proton is accompanied by the opening or closing of a ring it is called ring鈥揷hain tautomerism. This type of tautomerism is well observed in carbohydrates, but it also occurs in other molecules such as warfarin. In this work, we present an approach that allows for the generation of all ring鈥揷hain tautomers of a given chemical structure. Based on Baldwin鈥檚 Rules estimating the likelihood of ring closure reactions to occur, we have defined a set of transform rules covering the majority of ring鈥揷hain tautomerism cases. The rules automatically detect substructures in a given compound that can undergo a ring鈥揷hain tautomeric transformation. Each transformation is encoded in SMIRKS line notation. All work was implemented in the chemoinformatics toolkit CACTVS. We report on the application of our ring鈥揷hain tautomerism rules to a large database of commercially available screening samples in order to identify ring鈥揷hain tautomers.