JPH0564387B2 - - Google Patents

Description

[Detailed Description of the Invention] [Field of the Invention] The present invention relates to a method for recording and retrieving chemical reaction information using a computer, and more specifically, the present invention relates to a method for recording and retrieving chemical reaction information using a computer. The present invention relates to a method of recording and retrieving information to facilitate searching, consideration of similar compounds and reactions, and research on methods of synthesizing new compounds with similar chemical structures. [Technical background of the invention] In recent years, with the development of computers,
Various methods have been proposed and are being used to record structural information on chemical substances, especially organic compounds. A huge amount of organic compounds and organic chemical reactions have been studied and elucidated to date, but it is possible to effectively use this known information to quickly search for known chemical substances or chemical reactions. Furthermore, it is desired to find a method for synthesizing new substances having desired properties. To this end, computers can process chemical formulas (i.e., computers can make logical judgments) instead of conventional chemical structural formulas, which are easy for engineers to understand, as a form of expression for chemical substances and chemical reactions. There is a need to develop and utilize forms of expression (that are possible). WLN is the recording method for chemical substances.
Typical methods include linear notation (Wiswesser Linear Notation) and methods using join tables; details can be found in, for example, WTWipke, SR
Heller, R. J. Feldmann, E. Hyde (Eds):
“Computer Representation and Manipulation
of Chemical Information” (John Wiley and
Sons, New York, 1974).
For example, a connection table is a table that lists the type of each atom in the structural formula of a chemical substance, the atom to which it is bonded, and the type of bond. It has the advantage of being able to search for substances on an atomic basis. Methods for recording information regarding structural changes (chemical reactions) of chemical substances have also been proposed, but no satisfactory method of expression has been known so far. For example, one way to record information about chemical reactions is to use reaction codes.
Specifically, J. Valls, O. Scheiner: “Chemical
Information Systems”, E.Ash, E.Hyde (Eds),
(Ellis Horwood Limited, 1975) p.241-258, MALobeck, Angew.Chem.
Intern.Ed.Engl., 9 , 578 (1970), and HJZiegler, J.Chem.Inf.Comput.
Sci., 19 , 141 (1979). This method has a drawback in that it cannot record new chemical reactions when they are discovered, since the viewpoint of chemical reaction expression is fixed. Another drawback is that structural information on chemical substances and information on changes thereof are recorded in separate formats, making it impossible to perform effective information retrieval. Separately, a recording method devised from the standpoint of designing synthetic routes for chemical substances is also known. for example,
E.J.Corey, R.D.Cramer, W.J.Howe, J.Am.
Chem.Soc., 94 , 440 (1972), I.Ugi, J.Bauer.J.
Braodt, J. Friedrich, J. Gasteiger, L. Jochum,
W. Schubert, Angew.Chem.Intern.Ed.Engl.
18, 111 (1979). However, this method is not suitable for recording individual chemical reactions. [Summary of the Invention] An object of the present invention is to propose a new processing method for recording and retrieving information regarding structural changes of chemical substances using a computer. A further object of the present invention is to provide a processing method for recording and storing chemical information that integrates information regarding starting materials, product materials, and structural changes between them in an expression format that can be processed by a computer. It is. The present invention is a step of obtaining information regarding the structure of each of a starting material and a product of a chemical reaction in which at least one product is produced from at least one starting material; , (1) bonds between nodes that exist in common in the starting material and the product material,
(2) The process of separately representing the bonds between nodes that exist only in the starting material, and (3) the bonds between nodes that exist only in the product; A step of creating a structural diagram representing structural changes, or creating a connection table containing information about each node, the node to which the node is connected, and the connections between the nodes; a step of storing the recorded structure on a recording medium attached to the computer; and a step of searching for at least one of the chemical reaction, the starting material, and the product substance by processing the stored structure diagram or bonding table with a computer; How to record and search chemical reaction information. When implementing the above method for recording and retrieving compound reaction information, information regarding the structure of each starting material and product material is collected, including the type of each node in the starting material and product material, the two-dimensional or three-dimensional coordinates of the node, and the structure of the starting material and product material. It is advantageous to obtain this information as information including the connection multiplicity between nodes. In addition, when implementing the above chemical reaction information recording/search method, bonds between nodes in the bond table are represented by a pair of numbers (a, b) [where a is an integer representing the bond multiplicity in the starting material, and b is an integer representing the change in bond multiplicity in a chemical reaction. According to the method of the present invention, chemical reaction information is converted into a two-dimensional or three-dimensional structural diagram and/or a bonding table through arithmetic processing by a computer based on input information about each of the starting materials and product substances involved in the chemical reaction. can be obtained automatically. In the present invention, a structural diagram refers to structural changes of substances involved in a chemical reaction, including (1) bonds that exist only in the starting material, (2) bonds that exist only in the product material, and (3) bonds that exist in common to both. Figures that are distinguished into three types of bonds (this is called an ``imaginary transition structure'')
means. This structural diagram allows a chemical reaction to be represented in a form that is visually familiar and easily understandable to engineers in accordance with conventional structural formulas and three-dimensional structural diagrams of compounds. In addition, the connection table is a simple and clear list of combinations such as the type of node, the partner node that connects to the node, and the connections between these nodes that are classified into the three types mentioned above. Chemical reaction information can be accumulated and stored on a recording medium attached to a computer without requiring a large capacity. In the present invention, based only on information regarding chemical substances such as starting materials and produced substances, it is possible to derive systematic information about chemical reactions involving these substances through arithmetic processing by a computer. The resulting structure diagram or bond table concisely represents a chemical reaction, and can be said to be the optimal form for recording and storing (registering) enormous amounts of chemical reaction information. In other words, in these structural diagrams and bond tables, chemical reactions are basically expressed as simple expressions of bonds between nodes (nodes) consisting of atoms, atomic groups, etc., and Connections between nodes are expressed in the above three types. In other words, since the bonds connecting each node are represented in relation to the starting and product materials, structure diagrams and bond tables comprehensively contain information about the chemical reactions themselves as well as about the substances involved in the reactions. are doing. Therefore, compared to various conventional registration formats, these registration formats are extremely superior in that both chemical substance information and chemical reaction information can be recorded and stored at the same time. Chemical substances and chemical reactions can be searched and matched atomically using diagrams and/or bond tables. Further, by using the registration form obtained by the present invention, the information can be easily processed later by a computer, and does not require a large storage capacity. Since chemical reactions can be easily registered on a recording medium, it becomes easy to accumulate and manage this information. Additionally, based on chemical reaction information registered (saved) on a recording medium connected to a computer, it is possible to efficiently search for information on chemical reactions and chemical substances involved in the reactions in a short period of time. In order to collect information in each engineer's research,
It is possible to shorten the time required for investigations, etc., and increase the density of information obtained, making it possible to proceed with research efficiently. In addition, we also offer structural analysis and molecular design of chemical substances, which are in high demand for engineers involved in drug manufacturing.
modeling), organic synthesis route design (heuristic
It can be effectively used in applied fields such as analysis of organic synthesis. Furthermore, in the present invention, if the connection table also includes information about the spatial coordinates of each node, it is possible to arbitrarily convert between the structure diagram and the connection table, and any Chemical reactions can also be displayed and recorded in form. In addition to the above-mentioned advantages, for example, the bonds between each node can be represented by a pair of numbers (a, b) [where a is an integer representing the bond multiplicity in the starting materials and b represents the change in bond multiplicity in the chemical reaction]. When expressed as an integer], it is possible to represent not only individual reactions but also multiple consecutive reactions (multi-step reactions) together in one bond table, and any intermediate reactions and a series of Synthesis reactions can be easily displayed. Therefore, by using the structure diagram and/or connection table obtained by computer processing according to the method of the present invention,
Substructure search and structure of chemical substances and chemical reactions
Activity relationships, automatic structure determination of unknown compounds, and prediction of reaction mechanisms and reaction products when complex compounds are reacted under certain conditions (mechanistic
It is possible to carry out evaluation of organic reactions within a sufficiently practical range in a short period of time. [Detailed Description of the Invention] In the method for recording and retrieving chemical reaction information of the present invention, based on the input information regarding the structure of the starting material and the structure of the product material, these structures are first topologically transformed on a computer. After superposition, the bonds between nodes are distinguished into three types: bonds that exist only in the starting material, bonds that exist only in the product, and bonds that exist in common to both, and the structural changes of chemical substances in chemical reactions are investigated. Operations are performed that are represented in the form of structure diagrams (imaginary transition structures) and/or connection tables. The method of the present invention will be specifically explained by taking as an example a reaction in which ethyl acetate is hydrolyzed with hydrochloric acid. Chemical reaction example 1 Reaction of hydrolyzing ethyl acetate with hydrochloric acid This chemical reaction is represented by CH ₃ COOCH ₂ CH ₃ +H ₂ O+HCl → CH ₃ COOH+CH ₃ CH ₂ OH+HCl (reaction formula 1). All starting materials (original system) and all product materials (product system) involved in the reaction are represented by conventional structural formulas, and the nodes are numbered in order as shown below. However, the node numbers are assigned so that they correspond to each other in the original system and the generating system. generation system When carrying out the information processing of the present invention, material information regarding the structure of the starting material and product material is expressed in the form of a structural formula (two-dimensional structure) as described above, or in the form of a three-dimensional structure, which is easy for engineers to understand and judge. can be entered into a computer in the form of Alternatively, input information regarding the nodes of each substance and the connections between nodes individually as text information in an interactive format, such as "There is a connection with multiplicity 1 between node (1) and node (2)". You may. When inputting in the form of letters, numbers, etc., positional information such as two-dimensional or three-dimensional coordinates of each node can also be included. Based on this input information, the original system (starting material group) and the production system (product material group) are superimposed topologically, that is, in the same phase, using arithmetic processing in a computer. here,
Specifically, “overlapping topologically” means,
It refers to matching the nodes appearing in the structure of the starting material and the nodes appearing in the structure of the product material, and combining these structures into one. As a result, The structure represented by is obtained. Next, regarding the bonds between each node of structure 1', (i) bonds that exist in common in the starting material and product are represented by the symbol -, and (ii) bonds that exist only in the starting material are represented by the symbol +. , and (iii) If the bond that exists only in the product substance is represented by the symbol..., then The structure represented by is obtained. The obtained structure 1 is a two-dimensional structural diagram expressing the structural change of a substance involved in a chemical reaction, and in the present invention, it is called an imaginary transition structure.
structures (hereinafter abbreviated as ITS). In other words, an imaginary transition structure (ITS) is a two-dimensional structure in which the structure of the starting material and the structure of the generated material are topologically superimposed, and the bonds between each node are distinguished by the three types (i) to (iii) above. Or a three-dimensional structure. In addition to the two-dimensional imaginary transition structure as mentioned above,
Of course, it is also possible to create a three-dimensional imaginary transition structure based on three-dimensional structural information of a chemical substance. Therefore, when creating an imaginary transition structure, information regarding the relative spatial arrangement of each node (two-dimensional or three-dimensional coordinates) is input to the computer.
must be included. In the imaginary transition structure (ITS) according to the present invention, all atoms contained in the source system and the product system may be used as nodes of substances involved in chemical reactions, or methyl groups [the above node (1), (5)], or a methylene group [node (4) above]. Further, when expressing a chemical reaction, it is possible to partially omit some nodes appearing in the original system and the production system, and this is also included in the present invention. In addition, the distinction between the three types of bonds is not limited to the display using symbols such as those in (i) to (iii) above. For example, the display using simple characters such as numbers (1, 2, 3), or color Any means, such as color-coded display (black, red, green) that allows the user to judge using his five senses and that can be processed by a computer, may be used. Hereinafter, in the present invention, (i) a bond common to the starting material and the product material (symbol -) will be referred to as a "colorless bond", and (ii) a bond that exists only in the starting material (symbol +) will be referred to as an "outgoing bond". (iii) The symbols (symbols...) that exist only in generated substances are called "in bonds," and out bonds and in bonds are collectively called "colored bonds." Specifically, Table 1 summarizes the types of bonds that appear in the imaginary transition structure in the present invention. In addition, the first
In the table, the horizontal numbers mean indicators of inflows and outflows of bonds. [Table] In Table 1, for example, the bond represented by the symbol "..." is a single in-bond, and can be represented by a pair of numbers (0+1). Here, 0 means that no bond exists in the original system before the reaction, and +1 means that a single bond is present in the product system after the reaction. Similarly, the bond represented by "+" is a single out-bond and is represented by (1-1). This means that single bonds have disappeared in the system. In addition, the bond represented by (2-1) is a double bond singly
cleaved) and is written as "±". Thus the type of join is also a pair of numbers:
(a, b) [where a is an integer representing the bond multiplicity in the starting material, and b is an integer representing the change in the bond multiplicity in the chemical reaction], and in this case, the bond multiplicity is Even if the severity is 2 or more, it can be written concisely.
Note that in the notation of (a, b), the comma (,) may be omitted. In addition, this notation is particularly preferable for storing records of chemical reactions because it does not require much storage capacity and can be directly processed by a computer, and is preferably used when creating a bond table, which will be described later. It is a method of expression. Individual chemical reactions can be recorded (registered) in the form of two-dimensional or three-dimensional imaginary transition structures (figures) obtained in a recording medium attached to a computer. This registered form is very superior in that it is in the form of a structural formula or three-dimensional structural diagram that can be visually understood and judged immediately by those who wish to use the chemical reaction information. For example, from this registered imaginary transition structure, the structure of the starting material can be obtained by deleting only the incoming bonds (making them non-bonded), and the structure of the product material can be obtained by deleting only the outgoing bonds. In other words, the imaginary transition structure according to the present invention includes not only chemical reaction information but also chemical substance information, and this registered form can be used to perform not only reaction searches but also chemical structure searches. be. In addition, if only the colorless bonds are deleted in ITS1 above, the structure in which outbound bonds and inbound bonds are alternately connected [(2)−(3)+(10)−(11)+(8)−(7)+( 2)], which is called a reaction string.
Note that - and + here mean outgoing coupling and incoming coupling, respectively. The reaction term can be extracted as a form specific to each reaction type, and in this case, it is an expression specific to the ester hydrolysis reaction. That is, using the registered imaginary transition structure, it is possible to extract only reaction signs that are structural expressions specific to individual reaction types, and reaction searches can be made easier. In addition, it is also possible to extract only the ring structures (open or closed rings) that participate in the reaction. Alternatively, based on the above input information about the starting materials and the product materials, a connection table is created that includes information about each node, the binding partner node that binds to the node, and the connections between the nodes.
It is also possible to create a table and represent chemical reaction information as a bond table. First, after topologically superimposing the original system and the generating system, we express the connections between each node by distinguishing between colorless or colored connections and outgoing or incoming connections, and create an imaginary transition structure (Structure 1). . From the obtained imaginary transition structure, information about the type of each node, the type of partner node connected to each node, the type of connection between these nodes, and, if desired, the positional coordinates of each node in the form of numbers, letters, etc. Expressed as
Create a list that lists these in order of node number. Table 2 shows the bond table obtained for the hydrolysis reaction of the above ester. Note that the connection table also includes information regarding the two-dimensional coordinates (xy coordinates) of each node. [Table] [Table] As shown in Table 2, the bond table includes all nodes and their This is a list in which two-dimensional coordinates (node (1) is taken as the origin), all nodes connected to each node, and types of connections between these nodes are listed in order of node number. The coupling table can also be created directly from information input to the computer without creating an imaginary transition structure. In this case, "topological superposition" means not only to graphically superimpose the structure of the starting material and the structure of the generated material by matching the nodes, but also to compare and match the bonds between corresponding nodes of both structures. It also means to do. The individual chemical reactions can then be registered in the form of a bond table on a recording medium attached to the computer. This registration format is advantageous in that it does not require a large recording capacity and can be directly processed by a computer. Note that it is of course possible to register a combination of a bond table and an imaginary transition structure, which is preferred in the present invention. The connection table may also include input information regarding the position coordinates of each node, etc., as described above. Furthermore, the imaginary transition structure and/or bond table may include information regarding the charge and stereochemistry of each node; various physical property values of chemical substances involved in the reaction;
Spectral information; and information regarding the enthalpy of the reaction, temperature, time, catalyst used, atmosphere, reaction phase, reaction yield, presence or absence of by-products, etc. may be described. If the imaginary transition structure or bond table registered in a computer contains this additional information, the imaginary transition structure or bond table can be used as a database for chemical substance structure search systems, chemical reaction search systems, or organic synthesis. It can be widely used in design systems, etc. When registering the above-mentioned imaginary transition structure and/or bond table in a recording medium attached to a computer, in order to facilitate the accumulation, management, and retrieval of chemical reaction information, each imaginary transition structure and/or bond table is A number may be assigned, or a reaction name may be registered for each imaginary transition structure and/or bond table. Based on the registered bond table, it is possible to display starting materials, produced substances, reaction formulas, etc., and it is also possible to extract reaction formulas and rings involved in the reaction, as in the case of imaginary transition structures. It is.
Furthermore, by performing appropriate arithmetic processing on bonds represented by combinations of numbers (a, b), for example, it is possible to integrate reactions spanning multiple stages and display them as a single bond table. That is, it is possible to simply display not only individual reactions but also the entire complex reactions such as those in the synthesis of organic compounds, or to extract and display only a part of the reactions. Therefore, this registered bond table is used in a wide range of fields in which computers are used in chemistry, such as molecular design focusing on specific properties of substances, determination of synthetic routes for organic compounds, and automatic structure determination of unknown compounds. It can be used as a format. Conversely, it is also possible to create an imaginary transition structure based on the registered bond table, and in the various search systems mentioned above, it is possible to arbitrarily convert between the bond table and the imaginary transition structure for chemical reactions. can. This makes it possible to perform various searches even more easily, and it is possible to increase the versatility and usability of the search system. The imaginary transition structure and/or coupling table may be registered in the computer by storing it in the computer's main memory, or by storing it in a recording medium (magnetic disk, optical disk, etc.) connected to the computer by wire. , magnetic tape, etc.)
It may be recorded and saved via . The registered imaginary transition structure and/or bonding table can be recorded on various recording materials such as plain paper using an appropriate recording device, or displayed on a color cathode ray tube connected to a computer or electronic equipment. Below, the method for recording and retrieving chemical reaction information of the present invention will be further explained using another chemical reaction example. Chemical reaction example 2 Reaction of adding n-butyllithium to acetone This chemical reaction is It is expressed as An imaginary transition structure for the reaction was created based on the structural formulas of the starting materials and products. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 3. Note that the connection table also includes information regarding the two-dimensional coordinates (xy coordinates) of each node. [Table] Chemical reaction example 3 Acylation reaction by Friedel-Crafts reaction This chemical reaction is It is expressed as An imaginary transition structure for the reaction was created based on the structural formulas of the starting materials and products. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 4. Note that the connection table also includes information regarding the two-dimensional coordinates (xy coordinates) of each node. [Table] Chemical reaction example 4 Beckmann rearrangement This chemical reaction is It is expressed as An imaginary transition structure for the reaction was created based on the structural formulas of the starting materials and products. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 5. Note that the connection table also includes information regarding the two-dimensional coordinates (xy coordinates) of each node. [Table] Chemical reaction example 5 Methylation reaction of cycloheptanone This chemical reaction is a series of reactions A to C: It is expressed as (1) Regarding the A-stage reaction, an imaginary transition structure of the reaction was created based on the structural formulas of the starting materials and product materials. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 6. The connection table shows the two-dimensional coordinates (xy coordinates) of each node.
It also includes information about. [Table] (2) Regarding the B-stage reaction, an imaginary transition structure of the reaction was created based on the structural formulas of the starting materials and product materials. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 7. The connection table shows the two-dimensional coordinates (xy coordinates) of each node.
It also contains information about. [Table] [Table] (3) Regarding the C-stage reaction, an imaginary transition structure of the reaction was created based on the structural formulas of the starting materials and product materials. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 8. The connection table shows the two-dimensional coordinates (xy coordinates) of each node.
It also contains information about. [Table] [Table] (4) A and B stage reactions, i.e. We created an imaginary transition structure for the reactions based on the structural formulas of the starting materials and products. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 9. The connection table shows the two-dimensional coordinates (xy coordinates) of each node.
It also contains information about. [Table] (5) Reactions of A, B and C stages, i.e. We created an imaginary transition structure for the reactions based on the structural formulas of the starting materials and products. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 10. The connection table shows the two-dimensional coordinates (xy coordinates) of each node.
It also contains information about. 【table】

Claims (1)

[Scope of Claims] 1. Obtaining information regarding the structure of each starting material and product material of a chemical reaction that produces at least one product material from at least one starting material; Superimposed: (1) bonds between nodes that are commonly present in the starting material and product material;
(2) The process of separately representing the bonds between nodes that exist only in the starting material, and (3) the bonds between nodes that exist only in the product; A step of creating a structural diagram representing structural changes, or creating a connection table containing information about each node, the node to which the node is connected, and the connections between the nodes; a step of storing the recorded structure on a recording medium attached to the computer; and a step of searching for at least one of the chemical reaction, the starting material, and the product substance by processing the stored structure diagram or bonding table with a computer; How to record and search chemical reaction information. 2. A patent claim that obtains information regarding the structure of each of the starting material and the product material as information including the type of each node in the starting material and the product material, the two-dimensional or three-dimensional coordinates of the node, and the multiplicity of connections between the nodes. A method for recording and searching chemical reaction information as described in Scope 1. 3 The connections between nodes in the connection table are expressed as a pair of numbers (a,
b) [wherein a is an integer representing the bond multiplicity in the starting material, and b is an integer representing the change in the bond multiplicity in the chemical reaction] How to record and search chemical reaction information.