CHAOS program

Automatic processing module This module tries to apply to the target molecule a series of "transforms or "disconnections" defined in the program (these transforms are listed in Appendix B-3). A "transform", for the CHAOS program, consists of the following information ... 

Keeping all these considerations in mind, the "disconnections which the CHAOS program may perform have been classified into six different groups of decreasing priority ... 

Some comments on the concept of "transform " in the CHAOS program As we have said. Appendix B-3 shows all the "transforms" incorporated to CHAOS. The "retrons" are represented at the left side, and the result of their disconnection (the "synthons") appears at the right side. However, the user will... 

In the CHAOS program, the transforms also include some "optional" additional information (it has not been included for all of them only when it has been considered convenient). This type of information can be classified in two groups ... 

When designing the CHAOS program, we realised that the classification of the disconnections in groups of "decreasing priority" was not enough in order to obtain retrosynthesis of great interest. Such retrosynthesis could only be obtained if a "multi-step look-ahead" analysis was performed. For this reason we decided to create "sequences of disconnections". We define a sequence of disconnections as the set of retrosynthetic steps that have to be performed in order to apply an specific... 

Finally, we must deal honestly with the limitations and deficiencies of our CHAOS program. 

CHAOS is a program for the computer-assisted design of organic synthesis. CHAOSBASE is an auxiliary program, which makes it possible to create retrosynthetic reactions data bases that can then be used by the CHAOS program. 

On the disk labelled MACINTOSH VERSION there are two icons, one of which represents the CHAOS program and the other the CHAOSBASE program. This is what these icons look like ... 

The first part of the manual explains the running of the CHAOS program and the second, the CHAOSBASE program. We believe the best way to read the manual is in the order in which it is printed. 

To begin with, it is important to remember that the disconnections incorporated into the CHAOS program are grouped in order of decreasing priority. The program uses these groups in the following way ... 

When the CHAOS program is started up, the screen will look like the following figure ... 

When you want to erase completely a synthesis created by the CHAOS program, you must erase these two files which form a part of it. 

The syntheses which you have composed using the CHAOS program remain... 

Ask the CHAOS program to disconnect the target molecule using the disconnections existing in the data bases open at that moment. 

Observe how the synthesis tree has grown. As we have seen, the most common way of using the CHAOS program is ... 

The program includes a few characteristic disconnections from the field of heterocyclic chemistry, which can be activated via the option "PROCESS-(heterocyclic chemistry)". These have only been included as examples. The Tables corresponding to these connections can be found in Appendix B-3. If the user really wants to use the CHAOS program in the field of heterocyclic chemistry, we suggest he/she should construct a heterocyclic reactions data base using the CHAOSBASE program. 

The disconnections included in the CHAOS program are arranged in groups activated in order of decreasing priority. The program contains a fixed order of priority for the groups. However, the user can change this priority as follows ... 

For the CHAOS program to function with a previously created data base, you must first open it. The option "Open database" Database menu) brings up a dialog box with which you can locate and open the data base you want. 

The CHAOS program permits a maximum of 10 data bases to be open simultaneously. The data bases names will come up on the same Database menu, as the user opens them. If you have two data bases open, called "CHBASEl" and "CHBASE2," the menu will look like this ... 

Sequences of disconnections can be built by the CHAOSBASE program, analogous to those included in the CHAOS program. If CHAOS finds a sequence included in a data base, applicable to the target molecule, a dialog box will come up, which is very similar to the one in the last figure but also contains the buttons Last and Next. These buttons allow you to see the various intermediate precursors generated in the sequence. 

The CHAOS program can export pictures to other programs. To do this ... 

The option "Select" can be used to copy on the "clipboard" any figure appearing in the windows of the CHAOS program. For example, you can copy synthetic pathways obtained with the option "Synthetic sequence" (Process menu), synthesis trees, etc. 

Note The program does not allow figures to be imported from other programs ("Paste" option), as these figures would lack the structural information needed for the CHAOS program to perceive the functional groups, rings, etc. 

The CHAOSBASE program has been designed to create retrosynthetic reactions data bases, i.e. transforms data bases. These transforms can be used by the CHAOS program to create synthetic pathways. As many data bases as are needed can be created, but CHAOS can only use a maximum of 10 data bases simultaneously. 

The disconnections introduced into a data base will be used by the CHAOS program as follows CHAOS will search for groupings of atoms (substructures or retrons) in the target molecule and if it finds one of these retrons, it will try to... 

These attributes and restrictions are discussed later on in the manual. Sequences of disconnections can also be defined, so that several transforms are applied successively to the target molecule. Notes, bibliographic references, etc., linked to each reaction, can also be introduced. The CHAOS program lets the references linked to a transform be seen when it manages to disconnect a molecule using this transform. 

Observe how a double bond with one thin and one thick line has appeared, a graphic representation that this bond can be single or double in the target molecule. The CHAOS program will detect the presence of this substructure provided it finds either of the two atom groupings in the following figure ... 

Note CHAOSBASE does not prevent the introduction of substructures which are contradictory. It is possible, for example, to indicate that a nitrogen atom belongs to the functional group "Ketone". Nor does it prevent possible violations of valence. The consequences of defining an "impossible retron" are that the CHAOS program will never be able to detect its presence in the target molecule. 

CHBASEl where we will introduce the Diels-Alder reaction. It is important to do these exercises, as this data base is used in the part of the manual which deals with the CHAOS program. 

Create atom" creates an atom which is near the marked atom, but not joined to it. The behaviour of "Create atom" may seem a little odd. It has been introduced because you may sometimes want to show, alongside the precursors, some reagent which, for example, acts as a catalyst. The fact that this atom is located near in space to a previously marked atom is so that the CHAOS program can assign it some coordinates. 

To introduce new atoms, as already stated, you do not need to select any atom or bond simply follow the technique explained above when discussing the CHAOS program (press the button of the mouse near the atom at which you want to start drawing and, without releasing the button, drag the mouse to where you want the new atom. Once there, release the button). This technique can also be used to create bonds between atoms already on screen, but not joined directly. 

By taking all these steps you have defined a sequence of disconnections. When you use this data base with the CHAOS program, CHAOS will perform the following actions ... 

Note For the CHAOS program to perform successfully a "sequence of disconnections", the result of the disconnection (svnthon) corresponding to the "n" stage of the sequence must correspond exactly with the substructure (retron) of the "n+1" stage. The user must define and "link" (via the "Link" command) the disconnections correctly, in such a way that the resulting sequence makes sense to the CHAOS program. 

Note With the exception of the final stage, a transform must never be used in a sequence of disconnections which, on being applied, generates several fragments the CHAOS program will be unable of carrying through such a sequence. 

Note Sequences of up to ten linked disconnections can be defined. However, bear in mind that the time the CHAOS program needs to perform a sequence of this nature may be too long. 

Bear in mind that the CHAOS program views the sequences as a whole. Therefore, to show the user a sequence, the program must have been capable of performing the sequence right through to the last stage. 

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