Quick interface update per user feedback

Release 4.2.1

A thanks to user J.G. who wrote: "'Im a software engineer, not a chemist. Approaching this website with just memory from a basic college chemistry class many years ago, so "helpful/not helpful" is more like "what parts felt natural to use/easy to understand". That said, this is so well done that I actually opted into a survey about a website. Great software. Sorry I'm not proficient enough in the subject to offer much suggestion, but a point that slowed me down starting to try to make a molecule was that I saw carbon underneath the editor and first could not figure out how to drag that in to start (rather than starting with a skeleton on the left. Tutorial cleared that right up, though. If I have to start with a skeleton, perhaps hide the "Additions" section or make it look visibly disabled until a skeleton is used." 


I hope you don't mind me sharing your review! Per feedback, the additions panel now actually IS visibly disabled until the molecule has been created by first giving it a primary skeleton. This feedback is EXACTLY what we're looking for. Keep it coming!

Support for molecules with cycloalkane side chains, nested side chains, side chains with ether attachments, side chains attached to the parent skeleton with pi bonds and with atoms other than the first Carbon in the side chain, and introduction of support for the reactions used in the synthesis of pyrimethamine

Release 4.2.0

Perhaps the longest title of any entry thus far in the organic chem master blog. This update introduces support for, in general, molecules with more complex side chains. The main impetus for this update was actually to show the potential to take the power to unjustifiably and drastically raise prices for drugs like Daraprim away from greedy biotechnology CEOs like Martin Shkreli. Which of course is a very tall task, in no small part due to chemical patent restrictions, but hopefully the pathway synthesis search engine support added in this update will show a step in that direction and that one day the tool will be able to provide alternative synthesis pathways for important life saving medicines.

With that overarching goal in mind, the particular goal of this update was to empower the search engine to independently discover the same synthesis pathway to produce the drug Daraprim (pyrimethamine) that high school students in Sydney did in 2016. This pathway can be viewed in the image here: https://en.wikipedia.org/wiki/Pyrimethamine#/media/File:Pyrimethamine_traditional_synthesis.png .

The first step in achieving the discovery was to ensure that both the intermediate molecules involved in the synthesis and of course pyrimethamine itself were supported in both the interface and the search engine. The starting molecule, 1-chloro-4-(2-cyanoethyl)benzene, was actually already supported. The next intermediate molecule, 1-chloro-4-((2Z)-1-cyano-3-hydroxypent-2-en-2-yl)benzene, required adding support for side chains (in this case the 1-cyano-3-hydroxypent-2-en-2-yl radical) that were NOT attached to their parent chain at the first Carbon of the side chain. The proceeding intermediate molecule, the etherificated 1-chloro-4-((2Z)-1-cyano-3-methoxypent-2-en-2-yl)benzene, required adding support for side chains containing ethers. This of course leads to the concept of nested side chains! That is, the parent skeleton of a molecule can contain a side skeleton that itself contains a side skeleton. This was previously not allowed in the interface nor the search engine to keep the modeling simpler.

And, finally, support for the molecule pyrimethamine itself, or as know by its IUPAC name 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine. Support for this molecule specifically required adding support for side chains that are cycloalkanes which in turn required the introduction of an algorithm to determine which of two attached cycloalkanes should function as the primary skeleton. In particular, should the pyrimidine ring be considered the primary skeleton of the molecule or should the chlorobenzene ring be considered the primary skeleton.

As a side note, support was also added for molecules containing side skeletons bonded to the primary skeleton with a pi bond, such as propylidenecyclohexane.

After support for ALL intermediate molecules and the product was added, it was time to add support for the reactions. Support for the following three reactions was added to the pathway search engine: Ethyl propionate condensation, Diazomethane etherification, and Guanidine condensation.

And once all modifications were in place, the search engine was able to successfully "rediscover" the synthesis pathway of Daraprim.

Standards: Per usual, IUPAC naming rules were followed. In particular, the style for nomenclature used for radicals with a Carbon atom with a locant other than 1 attached to the parent skeleton was to use the locant followed by "-yl or -ylidine" as in (propan-2-yl)cyclohexane. The radical prefix "ylidine" was used to indicate the radical was attached to the parent via a double bond. The condensation reactions were modeled after the wikpedia article, employing the strong deactivation properties of the cyano group. The etherification via diazomethane reaction was also modeled after the wikipedia article.

Controls: No new controls were introduced. The user can still create the molecules via the molecule design tool or entering the IUPAC name in the interface and click the beaker icon to perform a synthesis pathway search.

Future Considerations: Hopefully even more power can be added to the pathway search engine via support for more complex molecules, more reactions, and more efficient search techniques in the future.