JPH0564386B2 - - Google Patents

Description

[Detailed Description of the Invention] [Field of the Invention] The present invention relates to the recording and retrieval of chemical reaction information using a computer, and more specifically, the invention relates to the recording and retrieval of chemical reaction information using a computer. record, search,
It also relates to methods for recording and searching to facilitate 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). Since this method has a fixed viewpoint for representing chemical reactions, it has the disadvantage that new chemical reactions cannot be recorded when they are discovered. 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 novel method for recording and retrieving information regarding structural changes of chemical substances using a computer. The present invention also records and records information regarding structural changes in chemical substances in an expression form that can be processed by a computer.
Its purpose is also to provide a method for searching. A further object of the present invention is to provide a method for recording and retrieving chemical reaction 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 provides a step of topologically superimposing the structure of a starting material of a chemical reaction producing at least one product from at least one starting material and the structure of the product; With the structure of the product, (1) bonds between nodes that exist in common in the starting material and the product;
(2) Create a structural diagram that expresses the structural change of a substance in a chemical reaction by displaying the bonds between nodes that exist only in the starting material and (3) the bonds between nodes that exist only in the product material. A step of recording and storing the chemical reaction, the starting material, and the produced material as the above structural diagram in a recording medium attached to a computer; Then, calculating the chemical reaction by computer processing from the recorded structural diagram. a step of searching for chemical reaction information;
It's in the search method. The present invention also provides a step of topologically superimposing the structure of the starting material and the structure of the product in a chemical reaction that produces at least one product from at least one starting material; Between the structure and the structure of the product, (1) bonds between nodes that exist in common in the starting material and the product;
(2) Bonds between nodes that exist only in the starting material, and (3) Bonds between nodes that exist only in the product material. A step of creating a bond table containing information regarding bonds; A step of recording and storing the chemical reactions, starting materials, and products as the bond table in a recording medium attached to a computer; and Retrieving the chemical reaction from a table by computer processing;
There is also a search method. When storing the bond table in implementing the above chemical reaction information recording/retrieval method, the structure diagram that expresses the structural change of the substance in the chemical reaction is also recorded and saved. It is advantageous to use a method of searching for said chemical reactions by computer processing from one or both of them. According to the method of the present invention, a chemical reaction is basically represented by a simple expression of nodes (nodes) consisting of atoms, atomic groups, etc. and the bonds between the nodes. Bonds between nodes in a reaction system can be 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, so only the chemical reaction itself can be expressed. Instead, it can also be expressed about substances such as starting materials and produced substances that are involved in the reaction. That is, compared to various conventional expression methods, the present invention allows both chemical substance information and chemical reaction information to be simultaneously recorded on a recording medium attached to a computer, such as a magnetic recording medium, an optical recording medium, or a magneto-optical recording medium. This is an excellent method in that it allows storage and retrieval of chemical reaction information. Further, by recording and storing chemical reaction information in a recording medium attached to a computer and then using the expression method according to the present invention when searching, the information can be easily processed by the computer, and it does not require a large storage capacity. Not at all. Since chemical reactions can be easily registered on a recording medium, it becomes easy to accumulate and manage this information. In addition, based on registered chemical reaction information, etc., it is possible to efficiently search for information on chemical reactions and chemical substances involved in the reactions in a short time, so engineers can collect information for their individual research. , it is possible to shorten the time required for investigations, etc., and increase the density of information obtained, allowing research to proceed efficiently. In addition, we also provide structural analysis of chemical substances, molecular modeling, and heuristic analysis of organic synthesis routes, which are in high demand for engineers involved in drug manufacturing.
It can be effectively used in application fields such as synthesis). Then, the chemical reaction information is recorded (registered) in a computer as a two-dimensional or three-dimensional structural diagram and/or a bonding table using the above expression method,
You can also search. In the present invention, a structural diagram refers to a diagram (this is called an "imaginary transition structure") that represents the structural change of a substance involved in a chemical reaction using the above-mentioned expression method. Based on the original structural diagram, chemical reactions can be represented in a form that is visually familiar and easy for engineers to understand. In addition, the bond table is a simple and clear list consisting of combinations of node types, partner nodes bonded to the nodes, and types of bonds between these nodes, and it does not require a large amount of capacity to store chemical reaction information. can be stored and stored on a recording medium connected to a computer. In both of these registration forms of structure diagrams and bond tables, the bonds connecting each node are expressed in relation to starting materials and product substances, so structure diagrams and bond tables are used to describe not only chemical reactions but also substances involved in reactions. It also contains comprehensive information. Therefore, chemical substances and chemical reactions can be searched and compared on an atomic basis using registered structural diagrams and/or bond tables. 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 bonding table of the present invention, storing it in a recording medium connected to a computer, and searching under desired conditions, it is possible to search for partial structures and structure of chemical substances and chemical reactions. -Activity relationships, molecular design, synthetic route design, 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. [Specific Description of the Invention] In the present invention, the structural change of a chemical substance in a chemical reaction is defined as a bond that exists only in the starting material when the structure of the starting material and the structure of the product are topologically superimposed, or a change in the structure of the chemical substance in the product. Three types of bonds can be expressed by distinguishing between them: bonds that exist only in one, and bonds that exist in common in both. Recording and retrieval of chemical reaction information according to the present invention will be explained using an example of 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). For all the starting materials (original systems) involved in the reaction, set nodes as shown below and number them in order. Hara system Next, when we superpose the original system (starting material group) and the product system (product material group) expressed by ordinary structural formulas topologically, that is, in the same phase, we get The structure represented by is obtained. where (i) the symbol - represents a bond that is present in common in the starting material and the product, (ii) the symbol + represents a bond that is present only in the starting material, and (iii) the symbol... It represents a bond that exists only in the product. In the present invention, the above structure 1 will be referred to as an imaginary transition structure (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. The product system obtained as a result of the hydrolysis reaction is
It is expressed by the following structural formula corresponding to the node number of the original system. generation system In other words, in the present invention, "topologically superimposing" means matching nodes appearing in the structure of the starting material and nodes appearing in the structure of the product material, and combining these structures. In the present invention, all atoms contained in the original system and the product system may be used as nodes of substances involved in the chemical reaction, or methyl groups [the above nodes (1) and (5)], methylene groups [the above An atomic group such as a functional group such as node (4)] may also be used. Also,
When expressing a chemical reaction, it is also possible to omit some nodes appearing in the original system and the production system, and this is also included in the present invention. In the imaginary transition structure (ITS) according to the present invention, the distinction between the three types of bonds is not limited to the symbols (i) to (iii) above; for example, numbers (1, 2, 3). Any means may be used as long as the user can make a judgment using the five senses and can be processed by a computer, such as display using simple characters such as , or color-coded display using colors (black, red, green). 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 of the present invention. Note that in Table 1, the horizontal numbers mean indicators of the inflow and outflow 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. Further, 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. Next, by focusing on the bonds between the nodes described above and using the expression method, we will explain each chemical reaction using the method described below, for example, on a magnetic recording medium, an optical recording medium, a magneto-optical recording medium, etc. attached to a computer. , recorded and stored on electromagnetic, optical, or a combination of these recording media. Recording of chemical reactions is carried out in the form of the above-mentioned telescopic structure, a bond table, or a combination thereof. If chemical reaction information is to be recorded and stored as an expression of an imaginary transition structure, first, in the above hydrolysis reaction of ethyl acetate with hydrochloric acid, the types of nodes (1) to (11) and the bonds between each node are A two-dimensional imaginary transition structure as shown in Structure (ITS) 1 is created based on input information about bonds that are colorless or colored and bonds that are distinguished as out or in bonds. Of course, it is also possible to create a three-dimensional imaginary transition structure.
Therefore, this connection information must include information (two-dimensional or three-dimensional coordinates) regarding the relative spatial arrangement of each node. Each chemical reaction is then registered in a computer in the form of the resulting two-dimensional or three-dimensional imaginary transition structure (figure). 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. When retrieving chemical reaction information recorded and stored in a recording medium equipped with a computer using the various expression methods described above, for example, only incoming bonds (no bonds) are deleted from this registered imaginary transition structure. ) gives the structure of the starting material,
Furthermore, by removing only the outgoing bonds, the structure of the product can be obtained. 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 compound structure searches. . In addition, when searching for recorded information, if only the colorless bonds are deleted in ITS1 above, a 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. In other words, when searching via a computer using the imaginary transition structure registered in the recording medium, it is possible to extract only the reaction code, which is a structural expression unique to each reaction type, which further improves the reaction search. It can be easily done. In addition, it is also possible to extract only the ring structures (open or closed rings) that participate in the reaction. When storing chemical reaction information in the form of a bond table on a recording medium attached to a computer, first record the type of each node in (1) to (11) in the above hydrolysis reaction of ethyl acetate with hydrochloric acid. Based on the input information about the connections that distinguish between colorless or colored connections and outgoing or incoming connections, information about each node, the connection partner node that connects to the node, and the connections between the nodes is calculated. Create a connection table containing The resulting combination table is shown in Table 2. 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 based on the imaginary transition structure described above. Alternatively, it is also possible to create a connection table through computer processing from information that has been directly input (that is, recorded or registered) into a recording medium connected to a computer in the form of an imaginary transition structure. Next, each chemical reaction is registered (recorded and saved) in a recording medium attached to the computer in the form of a bonding table. 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 (record and save) a combination of the connection table and the imaginary transition structure in a recording medium attached to a computer, which is preferable in the present invention. The connection table may also include input information regarding the spatial 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 properties of the 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 an imaginary transition structure or a bonding table registered (recorded and saved) in a computer storage medium contains such additional information, the imaginary transition structure or bonding table can be used as a database for chemical substance structure search systems and chemical reactions. It can be widely used in search systems, organic synthesis design systems, etc. When registering (recording and saving) the above-mentioned imaginary transition structure and/or bonding table in a computer recording medium, each imaginary transition structure and/or bonding table is A reaction 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 materials, reaction formulas, etc. through computer processing, and also extract the reaction formula and rings involved in the reaction in the same way as in the case of imaginary transition structures. It is also possible. Furthermore, by performing appropriate arithmetic processing using a computer on the bonds represented by combinations of numbers (a, b), it is possible to integrate reactions spanning multiple stages and display them as a single bond table. It is. 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 by computer processing based on the registered bond table, and in the various search systems mentioned above, the bond table and the imaginary transition structure can be arbitrarily mutually exchanged for chemical reactions. can be converted. Due to this,
It is possible to make various searches even easier,
It is possible to increase the versatility and usability of the search system. The imaginary transition structure and/or the coupling table may be registered in the computer by storing it in the main memory of the computer, or by storing it in a suitable recording medium (magnetic disk, magnetic disk, etc.) connected to the computer by wire. It may also be recorded and saved via an optical disk, magnetic tape, etc.). 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 The imaginary transition structure of the reaction can be expressed as follows. 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 Alcylation reaction by Friedel-Crafts reaction This chemical reaction is It is expressed as The imaginary transition structure of the reaction can be expressed as follows. 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 The imaginary transition structure of the reaction can be expressed as follows. 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) The reaction imaginary transition structure of the A stage can be expressed as follows. 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 contains information about. [Table] (2) The imaginary transition structure of the B-stage reaction can be expressed as follows. 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) The imaginary transition structure of the C-stage reaction can be expressed as follows. 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. The imaginary transition structure that summarizes the reactions consisting of can be expressed as follows. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 9. In addition,
The connection table also includes information regarding the two-dimensional coordinates (xy coordinates) of each node. [Table] (5) Reactions of A, B and C stages, i.e. The imaginary transition structure that summarizes the reactions consisting of can be expressed as follows. We also created a bond table corresponding to this imaginary transition structure. The resulting combination table is shown in Table 10. In addition,
The connection table also includes information about the two-dimensional coordinates (xy coordinates) of each node. 【table】

Claims (1)

[Claims] 1. A step of topologically superimposing the structure of a starting material and the structure of a product in a chemical reaction that produces at least one product from at least one starting material; the topologically superimposed starting materials and the structure of the product, (1) bonds between nodes that exist in common in the starting material and the product;
(2) Create a structural diagram that expresses the structural change of a substance in a chemical reaction by displaying the bonds between nodes that exist only in the starting material and (3) the bonds between nodes that exist only in the product material. A step of recording and storing the chemical reaction, the starting material, and the produced material as the above structural diagram in a recording medium attached to a computer; Then, calculating the chemical reaction by computer processing from the recorded structural diagram. a step of searching for chemical reaction information;
retrieval method. 2. A step of topologically superimposing the structure of the starting material and the structure of the product in a chemical reaction that produces at least one product from at least one starting material; the topologically superimposed structure of the starting material and the product. (1) Bonds between nodes that exist in common in the starting material and the product material,
(2) Bonds between nodes that exist only in the starting material, and (3) Bonds between nodes that exist only in the product material. A step of creating a bonding table containing information regarding bonds; A step of recording and storing the chemical reactions, starting materials, and produced substances as the bonding table in a recording medium attached to a computer; and a step of recording and storing the above recorded structure. A step of retrieving the chemical reaction from the diagram by computer processing;
retrieval method. 3. When storing the record of the bond table, a structural diagram representing the structural change of a substance in a chemical reaction is also recorded and saved, and the chemical reaction can be calculated from either or both of the bond table and the structural diagram that have been stored. A method for recording and searching chemical reaction information according to claim 2, which searches for.