Release 2.8.0
The main driving motivation of this update was to introduce interface support for another commonly used pharmaceutical drug, aspirin (2-acetoxybenzoic acid), as well as two new reactions so the pathway generator could again "discover" a well-known, existing synthesis pathway for aspirin. Aspirin was chosen because, similar to the already supported Tylenol (generically paracetamol or acetaminophen), aspirin can be synthesized as a derivative of phenol. Furthermore, aspirin, like Tylenol, is also on the World Health Organization's list of essential medicines.
In order for the interface to support the aspirin molecule, basic support for ethers needed to be introduced.* One particularly challenging aspect of adding support for nomenclature of ethers was the case where the user modifies the molecule enough to change which of the two alkane chains attached to the Oxygen should be regarded as the main chain. For example, if the user were to create the molecule 2-methoxyethane then add an ethyl group to the methyl side chain, thus expanding it to become a propyl chain, the interface would need to properly update the IUPAC name to 1-ethoxypropane, reflecting that the propyl chain is now the main chain per IUPAC rules.
Once ether support was in place, the benzoic acid and acetyl common IUPAC naming substitutions were added to the interface naming engine. Afterwards, the interface fully supported aspirin and the intermediates in an existing synthesis pathway.
The synthesis pathway to be "discovered" by the pathway generator involved two reactions: 1) carboxylation of phenol to produce salicylic acid (coincidentally also on the WHO's list of essential medicines), known as the Kolbe-Schmitt reaction, and 2) acetylation of salicylic acid to produce 2-acetoxybenzoic acid. Fortunately, providing support for the acetylation reaction was straightforward enough by simply adding a new rule to the existing acetylation reaction used in the synthesis of Tylenol to allow acetylation of a hydroxyl group. The Kolbe-Schmitt reaction was modeled to introduce a carboxyl group at an ortho position to the hydroxyl group in phenol.
With support for the two new reactions in place, the pathway generator could now officially solve for a pathway between phenol and aspirin!
During this process, it occurred to me that a convenient feature would be to search either Google or the Pub Chem database for information about the molecule as the user was creating it in the interface. Therefore, I added two buttons in the "Molecule Properties" section that can be clicked to perform a cross-reference search. In fact, if the user clicks the Google icon button while viewing 2-acetoxybenzoic acid, the user will indeed see links to articles about aspirin.
Finally, two minor interface tweaks were implemented. One involves a more correct highlighting feedback of the atom to which a dragged skeletal element will be attached as it is dragged over that atom. The other involves cleaning up a previously occurring "ghost trace" phenomenon for the dragging of large molecules. Dragging the position of the molecule in the workspace is now clean.
Standards- Per normal, IUPAC nomenclature standards were followed. Of particular interest, the following substitution of common IUPAC names were introduced: "benzene-1-carboxylic acid" and "benzenecarboxylic acid" are now substituted with "benzoic acid" and "(1-formylethoxy)" is substituted with "acetoxy". The length of both chains is used for determining the main chain and the side chain in an ether linkage between two chains. In the future, more complicated rules may be introduced as tiebreakers and for molecules with multiple ether linkages.
Controls- The user feedback in the form of highlighting of the atom to be attached to when the user drags a skeletal attachment over an atom has been improved to be more accurate. Also, two new icon buttons are present: a Google icon button and a Pub Chem icon button. Clicking either will cause a search of the respective engine in a new browser window.
Future Considerations- Support for ester linkages will certainly be upcoming soon. Also with more and more reactions being supported now by the pathway search engine, it is apparent that a page in the interface to view the rules followed by these reactions would be very helpful for further understanding. Finally, per a previous future consideration, it is again apparent that the ability to add more complex radicals to a molecule in the interface would be very helpful. Aspirin could be created, for example, by dropping a phenol in the workspace, then dropping an acetyl group on the Oxygen, and finally dropping a carboxylic acid group on a carbon in benzene adjacent to the one containing the ether linkage.
* Note: As the IUPAC naming for aspirin considers the molecule as an acetyl group bonded by an ether linkage to benzoic acid as opposed to an ester linkage between a benzoic acid and an ethyl group, we do NOT need to add support for esters in this update. Ester support will be done in the future, certainly.
The main driving motivation of this update was to introduce interface support for another commonly used pharmaceutical drug, aspirin (2-acetoxybenzoic acid), as well as two new reactions so the pathway generator could again "discover" a well-known, existing synthesis pathway for aspirin. Aspirin was chosen because, similar to the already supported Tylenol (generically paracetamol or acetaminophen), aspirin can be synthesized as a derivative of phenol. Furthermore, aspirin, like Tylenol, is also on the World Health Organization's list of essential medicines.
In order for the interface to support the aspirin molecule, basic support for ethers needed to be introduced.* One particularly challenging aspect of adding support for nomenclature of ethers was the case where the user modifies the molecule enough to change which of the two alkane chains attached to the Oxygen should be regarded as the main chain. For example, if the user were to create the molecule 2-methoxyethane then add an ethyl group to the methyl side chain, thus expanding it to become a propyl chain, the interface would need to properly update the IUPAC name to 1-ethoxypropane, reflecting that the propyl chain is now the main chain per IUPAC rules.
Once ether support was in place, the benzoic acid and acetyl common IUPAC naming substitutions were added to the interface naming engine. Afterwards, the interface fully supported aspirin and the intermediates in an existing synthesis pathway.
The synthesis pathway to be "discovered" by the pathway generator involved two reactions: 1) carboxylation of phenol to produce salicylic acid (coincidentally also on the WHO's list of essential medicines), known as the Kolbe-Schmitt reaction, and 2) acetylation of salicylic acid to produce 2-acetoxybenzoic acid. Fortunately, providing support for the acetylation reaction was straightforward enough by simply adding a new rule to the existing acetylation reaction used in the synthesis of Tylenol to allow acetylation of a hydroxyl group. The Kolbe-Schmitt reaction was modeled to introduce a carboxyl group at an ortho position to the hydroxyl group in phenol.
With support for the two new reactions in place, the pathway generator could now officially solve for a pathway between phenol and aspirin!
During this process, it occurred to me that a convenient feature would be to search either Google or the Pub Chem database for information about the molecule as the user was creating it in the interface. Therefore, I added two buttons in the "Molecule Properties" section that can be clicked to perform a cross-reference search. In fact, if the user clicks the Google icon button while viewing 2-acetoxybenzoic acid, the user will indeed see links to articles about aspirin.
Finally, two minor interface tweaks were implemented. One involves a more correct highlighting feedback of the atom to which a dragged skeletal element will be attached as it is dragged over that atom. The other involves cleaning up a previously occurring "ghost trace" phenomenon for the dragging of large molecules. Dragging the position of the molecule in the workspace is now clean.
Standards- Per normal, IUPAC nomenclature standards were followed. Of particular interest, the following substitution of common IUPAC names were introduced: "benzene-1-carboxylic acid" and "benzenecarboxylic acid" are now substituted with "benzoic acid" and "(1-formylethoxy)" is substituted with "acetoxy". The length of both chains is used for determining the main chain and the side chain in an ether linkage between two chains. In the future, more complicated rules may be introduced as tiebreakers and for molecules with multiple ether linkages.
Controls- The user feedback in the form of highlighting of the atom to be attached to when the user drags a skeletal attachment over an atom has been improved to be more accurate. Also, two new icon buttons are present: a Google icon button and a Pub Chem icon button. Clicking either will cause a search of the respective engine in a new browser window.
Future Considerations- Support for ester linkages will certainly be upcoming soon. Also with more and more reactions being supported now by the pathway search engine, it is apparent that a page in the interface to view the rules followed by these reactions would be very helpful for further understanding. Finally, per a previous future consideration, it is again apparent that the ability to add more complex radicals to a molecule in the interface would be very helpful. Aspirin could be created, for example, by dropping a phenol in the workspace, then dropping an acetyl group on the Oxygen, and finally dropping a carboxylic acid group on a carbon in benzene adjacent to the one containing the ether linkage.
* Note: As the IUPAC naming for aspirin considers the molecule as an acetyl group bonded by an ether linkage to benzoic acid as opposed to an ester linkage between a benzoic acid and an ethyl group, we do NOT need to add support for esters in this update. Ester support will be done in the future, certainly.
