{"action":"created","issue":{"url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/53","repository_url":"https://api.github.com/repos/OpenSourceMalaria/Series4","labels_url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/53/labels{/name}","comments_url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/53/comments","events_url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/53/events","html_url":"https://github.com/OpenSourceMalaria/Series4/issues/53","id":332290042,"node_id":"MDU6SXNzdWUzMzIyOTAwNDI=","number":53,"title":"2018 SSP Compounds","user":{"login":"edwintse","id":18062981,"node_id":"MDQ6VXNlcjE4MDYyOTgx","avatar_url":"https://avatars3.githubusercontent.com/u/18062981?v=4","gravatar_id":"","url":"https://api.github.com/users/edwintse","html_url":"https://github.com/edwintse","followers_url":"https://api.github.com/users/edwintse/followers","following_url":"https://api.github.com/users/edwintse/following{/other_user}","gists_url":"https://api.github.com/users/edwintse/gists{/gist_id}","starred_url":"https://api.github.com/users/edwintse/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/edwintse/subscriptions","organizations_url":"https://api.github.com/users/edwintse/orgs","repos_url":"https://api.github.com/users/edwintse/repos","events_url":"https://api.github.com/users/edwintse/events{/privacy}","received_events_url":"https://api.github.com/users/edwintse/received_events","type":"User","site_admin":false},"labels":[{"id":645880704,"node_id":"MDU6TGFiZWw2NDU4ODA3MDQ=","url":"https://api.github.com/repos/OpenSourceMalaria/Series4/labels/Question","name":"Question","color":"cc317c","default":false}],"state":"open","locked":false,"assignee":{"login":"edwintse","id":18062981,"node_id":"MDQ6VXNlcjE4MDYyOTgx","avatar_url":"https://avatars3.githubusercontent.com/u/18062981?v=4","gravatar_id":"","url":"https://api.github.com/users/edwintse","html_url":"https://github.com/edwintse","followers_url":"https://api.github.com/users/edwintse/followers","following_url":"https://api.github.com/users/edwintse/following{/other_user}","gists_url":"https://api.github.com/users/edwintse/gists{/gist_id}","starred_url":"https://api.github.com/users/edwintse/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/edwintse/subscriptions","organizations_url":"https://api.github.com/users/edwintse/orgs","repos_url":"https://api.github.com/users/edwintse/repos","events_url":"https://api.github.com/users/edwintse/events{/privacy}","received_events_url":"https://api.github.com/users/edwintse/received_events","type":"User","site_admin":false},"assignees":[{"login":"edwintse","id":18062981,"node_id":"MDQ6VXNlcjE4MDYyOTgx","avatar_url":"https://avatars3.githubusercontent.com/u/18062981?v=4","gravatar_id":"","url":"https://api.github.com/users/edwintse","html_url":"https://github.com/edwintse","followers_url":"https://api.github.com/users/edwintse/followers","following_url":"https://api.github.com/users/edwintse/following{/other_user}","gists_url":"https://api.github.com/users/edwintse/gists{/gist_id}","starred_url":"https://api.github.com/users/edwintse/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/edwintse/subscriptions","organizations_url":"https://api.github.com/users/edwintse/orgs","repos_url":"https://api.github.com/users/edwintse/repos","events_url":"https://api.github.com/users/edwintse/events{/privacy}","received_events_url":"https://api.github.com/users/edwintse/received_events","type":"User","site_admin":false}],"milestone":null,"comments":14,"created_at":"2018-06-14T07:54:59Z","updated_at":"2018-07-16T14:18:46Z","closed_at":null,"author_association":"CONTRIBUTOR","body":"For the past 4 years, the first year Special Studies Program here at the University of Sydney have been synthesising new Series 4 compounds. This year, their target compounds were based around modification of the RHS aryl group with non-aromatic heterocycles (highlighted in green).\r\n\r\n![untitled wiley-10](https://user-images.githubusercontent.com/18062981/42740809-79c9984e-88ef-11e8-99c2-7e1c11adfa92.jpeg)\r\n\r\nThe synthesis plan followed the typical route. The initial hydrazine SM was provided to them by us. This was then condensed with a commercially available CHO, cyclised and finally coupled with 2-phenylethanol.\r\n![untitled wiley-5](https://user-images.githubusercontent.com/18062981/41395912-aa0296d4-6ff2-11e8-8560-adbbdd134a26.jpeg)\r\nUpon completion of the synthesis in the undergrad labs, I made attempts at purifying their crude products. This is where things became problematic... I ran the 4 compounds through 3 Isolera columns each (1 regular, 2 reverse phase), however none of the compounds ended up clean. Either the aliphatic region was still broad and messy or the aromatic region still had multiple impurity peaks, both of which I would have expected reverse phase to have cleaned up. I suspect that this may have been due to the a couple of reasons: Reactions could only be performed once a week within the timeframe of the 3 h lab. Reactions were left sitting until the next weeks lab session. Crude material was taken through for each step from the beginning.\r\n\r\n**Good news**\r\n–––––––––––––––\r\n I ended up resynthesising the 4 compounds with purifications of each intermediate before subsequent steps. The two protected amines were also deprotected to give a total of 6 compounds that will be sent for evaluation tomorrow. My ELN entries are [here](https://au-mynotebook.labarchives.com/share/Edwin%2520Tse/OTUxLjZ8MTUwOS83MzIvVHJlZU5vZGUvOTIzNjgyMDY1fDI0MTUuNg==).\r\n\r\n**Not so good news**\r\n–––––––––––––––\r\nA comparison of their final products and the ones that I made are **not consistent**. In the spectra below, their compounds (after the 3 columns) are on top in blue and mine are below in red. It is clear that there are a number of differences between the spectra.\r\n- The signals in the aliphatic region don't match for any compounds.\r\n- The CH2 triplets appear to be absent in their samples.\r\n- The pyrazine singlet ~9 ppm is slightly shifted upfield in their compounds.\r\n- The phenyl multiplet is shifted slightly downfield in their compounds.\r\n\r\nIt is evident from this that they seem to have actually not made the desired compounds but something different.\r\n![ssp comparison1](https://user-images.githubusercontent.com/18062981/41397155-a40c46e0-6ff6-11e8-8e1d-75b2ec5452b0.jpg)\r\n![ssp comparison2](https://user-images.githubusercontent.com/18062981/41397156-a4357812-6ff6-11e8-8775-2dddffa8b979.jpg)\r\n![ssp comparison3](https://user-images.githubusercontent.com/18062981/41397157-a45f4016-6ff6-11e8-9976-4e85a0dd5e5b.jpg)\r\n![ssp comparison4](https://user-images.githubusercontent.com/18062981/41397159-a48ebf6c-6ff6-11e8-89ab-c3fbea9ee724.jpg)\r\nThe only characterisation that the students performed was a 1H NMR of their crude condensation products. Comparison of these NMRs has identified yet another inconsistency. Again, their compounds are on top in blue and mine are below in red.\r\n- In this case, all signals appear consistent between mine and theirs **except for one**.\r\n- One signal in the aromatic region is shifted upfield in their spectra (highlighted in the black boxes).\r\n- This is likely the NH proton considering the broadness.\r\n\r\nThe only explanation for this is that they've somehow **made the other isomer** of the condensation product. The only difference between the reaction conditions is that they used E95 ethanol and I used E100 ethanol but I'm not sure how this would have made such a difference. No recrystallisations were done in either case. This may have also have influenced them not making the final products, however, I'm again not sure how this would have affected the subsequent cyclisation?\r\n![ssp comparison 1](https://user-images.githubusercontent.com/18062981/41397987-3b28e89c-6ff9-11e8-857e-5edede82352e.jpg)\r\n![ssp comparison 2](https://user-images.githubusercontent.com/18062981/41397986-3afdcb80-6ff9-11e8-8fe3-9b1c20d81b5a.jpg)\r\n![ssp comparison 3](https://user-images.githubusercontent.com/18062981/41397985-3ad19e52-6ff9-11e8-8752-0eb88b6d205c.jpg)\r\n![ssp comparison 4](https://user-images.githubusercontent.com/18062981/41397984-3aa4125c-6ff9-11e8-9315-2da5cd26e2c4.jpg)\r\nI will look into the possibility that this could be due concentration dependence of the NMR samples to see if there's any shift in that signal. I will also get LRMS of their compounds to see if it matches."},"comment":{"url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/comments/405262996","html_url":"https://github.com/OpenSourceMalaria/Series4/issues/53#issuecomment-405262996","issue_url":"https://api.github.com/repos/OpenSourceMalaria/Series4/issues/53","id":405262996,"node_id":"MDEyOklzc3VlQ29tbWVudDQwNTI2Mjk5Ng==","user":{"login":"bendndi","id":36627399,"node_id":"MDQ6VXNlcjM2NjI3Mzk5","avatar_url":"https://avatars3.githubusercontent.com/u/36627399?v=4","gravatar_id":"","url":"https://api.github.com/users/bendndi","html_url":"https://github.com/bendndi","followers_url":"https://api.github.com/users/bendndi/followers","following_url":"https://api.github.com/users/bendndi/following{/other_user}","gists_url":"https://api.github.com/users/bendndi/gists{/gist_id}","starred_url":"https://api.github.com/users/bendndi/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/bendndi/subscriptions","organizations_url":"https://api.github.com/users/bendndi/orgs","repos_url":"https://api.github.com/users/bendndi/repos","events_url":"https://api.github.com/users/bendndi/events{/privacy}","received_events_url":"https://api.github.com/users/bendndi/received_events","type":"User","site_admin":false},"created_at":"2018-07-16T14:18:45Z","updated_at":"2018-07-16T14:18:45Z","author_association":"NONE","body":"I've just looked at the mas specs @edwintse  linked above - are these for the final compounds? If so, what is the mass ion you're seeing which suggests its the correct set of structures? Not being familiar with your MS system its difficult to know what we're looking at :-) \r\n\r\nI'm seeing some pretty high MW ions (e.g. in MS for 4d) which suggest dimerisation type structures (some of which still contain the Cl 35/37 fingerprint...)"}}
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