Reaction-Based Enumeration Panel — Choose Reaction Step

Set up the reaction or reaction sequence. Three methods are available for creating the reaction sequence: PathFinder analysis, which decomposes a structure by looking for reactions to synthesize it; choice of reactions from a library of reactions; and sketching the reaction sequence in the Sketcher.

See Reaction-Based Enumeration Panel for an overview of the panel.

  • Features
  • Additional Resources

Choose Reaction Step Features

Get reaction from options

Choose a source for the reaction:

  • PathFinder analysis—use the PathFinder tool to analyze a structure for possible synthetic routes to this structure, and choose the desired route for enumeration.

  • Reaction library—set up a sequence of reactions by choosing from a library of known reactions.

  • New sketch—sketch the reaction or reaction sequence in the sketcher.

The features displayed in the rest of the step depend on the choice of reaction source.

PathFinder analysis features

The PathFinder analysis analyzes a molecule to find reactions that could be used to synthesize it. This is done by splitting the molecule into two fragments that are reactants in known reactions that produce the molecule. The process is repeated for the fragments, recursively, up to a specified depth.

Options

Specify options for the PathFinder analysis.

Max depth text box

Specify the maximum depth of the PathFinder reaction analysis. This is the number of recursions performed by feeding reactant molecules from the previous analysis into PathFinder again. A depth of 1 means that only the original molecule is analyzed; a depth of 2 means that the reactants that produce the original molecule are also analyzed to find reactions that produce them., and so on.

Display Breakable Bonds button

Mark the bonds in the displayed structures that are considered breakable for enumeration. If the maximum depth is greater than 2, a progress bar may be displayed.

Once the bonds are marked, you can click to select any one fragment to exclude from the enumeration; Shift+click to auto-select other regions. The fragment boundaries are defined by the breakable bonds. Editing the structure also clears the marked region.

Limit to purchasable materials option

Enable this option to limit the reaction or analysis to purchasable materials only.

Use compound from option menu

Specify the source of the compound for the analysis:

  • Project Table (selected entry)—Use the entry that is currently selected in the Project Table. Only one entry must be selected.
  • Workspace—Use the entry that is currently included in the Workspace. Only one entry must be included in the Workspace.
  • File—Read the structure from a file. When this option is selected, the Browse button is displayed. Click Browse and navigate to the file you want to use. The first structure in the file is used, so you should ensure that this structure is a ligand-sized molecule.
  • New Sketch—Sketch the compound in the Sketcher.
Load or Browse button

Load the compound from the chosen source into the sketcher for modification and analysis. The Browse button opens a file selector to load the compound from a file. The button is absent when you choose New Sketch for the compound source.

Sketcher

The sketcher displays the compound as a 2D structure. If you loaded the compound from the Workspace, the Project Table, or a file, there is a button at the top left that you click to edit the structure in the Sketcher. When you do, the sketching tools are displayed. These tools are automatically displayed if you chose New Sketch for the compound source, and the button is absent.

Reaction library features

These features allow you to set up a sequence of reactions to produce a final product, by selection from a library of reactions. The library is obtained from the installation and supplemented with reactions that you define.

Options

Specify options for the reaction library

Import Reaction button

Import a reaction into the reaction table. Opens a file selector, in which you can import reactions from a reaction library file (.json) or a reaction file (.rxn).

Search bar

Filter the list of reactions to show only those containing the text you enter as part of the reaction name, the reactants, or the description of the reaction (e.g. Buchwald).

Table of available reactions

Lists the reactions available for selection, showing the reaction name and the reactants. You can filter the table using the search bar. The table lists the standard reactions from the installation, any reactions you have defined and stored in your user resources area, and any that you import. When you select a reaction, it is displayed below the table.

Current reaction

The reaction that is selected in the table is displayed below the table, with the reaction name above it and a description below it. Above the reaction display to the right are an Add button to add the reaction to the Reactions table, deselect the reaction (thus removing the display), and a more button (with dots on it) , which allows you to delete or edit the reaction if it is not one of the standard reactions, duplicate and edit a standard reaction, or export the reaction to a file. The editing is done in the Sketcher: the selection under Get reaction from switches to New sketch, and you can then edit the reaction. When you are done, select Reaction library again to return to the reaction library workflow and continue with the edited reaction.

Reactions table

The reactions sequence is displayed in this table. You can select a single reaction in the table. To the right are buttons for moving the selected step up or down in the sequence, editing the reaction (if it is not a standard reaction), and deleting the reaction from the sequence. There is a splitter (horizontal line of dots) above the table that you can drag vertically to resize the areas for this table and the available reactions table.

New sketch features

Sketch the structures using the 2D sketcher. A blank template for the reactions is shown in the Sketcher area.

Options

Specify options for sketching reactions.

Reaction steps text box

Specify the number of steps in the reaction sequence. The Sketcher divides into the specified number of steps, in each of which you sketch one reaction.

Sketcher

Sketch the reactions using the 2D Sketcher tools. For details on these tools, see 2D Sketcher Panel. The arrows are added automatically, and you should sketch the reactants on the left and the product on the right. When you add a second reactant or product, a plus sign is inserted automatically.

Save to Reaction Library button

Save the reaction to your default reaction library set, which is stored in your User resources directory. Opens the Save Reaction Dialog Box.

More Actions option menu

Choose other actions to perform.

  • Import—import a set of reactions into the Sketcher, which you can then edit. Opens a file selector to choose a reactions file.

  • Export—export the current set of reactions to a reactions file. Opens a file selector to name the reactions file.

  • Edit Reaction SMARTS—Edit the reaction SMARTS pattern for the sketched reactions. Opens the Reaction SMARTS dialog box, in which you can edit the reaction SMARTS pattern for each reaction in the sketch separately.

Generate Pathways button
Define Reactants button

Click this button to proceed to the next step. The button label (and the next step) depends on the choice you made under Get reaction from.

If you selected PathFinder analysis, the next step is Generate Pathways. This step is transient, and displays progress bars for the analysis and generation steps, if the analysis takes more than a few seconds. When the analysis is done, the Review Pathways step is displayed. You can stop the analysis and continue to the next step with the results obtained so far by clicking the Review Pathways button under the progress bars. This also allows you to go back and adjust the PathFinder options, for example, to reduce the depth of the analysis.

Otherwise the next step is Define Reactants, which is defining the reactant sets for enumeration.

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