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24th November 2014 @ 10:40

Solubility is becoming an increasingly crucial aspect of design in OSM Series 4, and a major outcome of the latest meeting

OSM Online Project Meeting 9 (24th Nov 2014)

was to ensure that all compounds being made have a healthy predicted logP value of below 3.5 or so.

It's important we are predicting these values accurately for proposed molecules. I'll shortly post what we know of the correlation between reality and prediction for OSM compounds. We have Chemdraw available to us, and are typically using this, and typically looking at the CLogP value. In tinkering with these calculations I previously noticed that drawing in explicit H's can give striking differences in these predicted values, in what is a known Chemdraw bug.

Explicit H's and Chemdraw ClogP

In tinkering a little more just now I also found that the predicted values are sensitive to explict H's on heteroatoms too, i.e. whether the H is draw as attached (N-H) or implicit (NH). Which tautomer is drawn also impacts significantly on the calculated value, though less so for LogP (rather than CLogP). This is more reasonable, but given that we have, below, four representations of what is one compound in solution, it's important we are aware of such variance (3.32 to 6.50) when using calculated values as a criterion for whether to make a given compound.

Chemdraw CLogP and Tautomers

Attached Files
15th November 2014 @ 22:05

OSM is now lucky enough to include chemists from Sydney Grammar School, who are making some much-needed molecules in Series 4. Alice already welcomed them on board here and here. Our intrepid explorers are Jason Chami, Evan Hockings, William Talbot, Sebastian Schwartz, Hugh Russell, James Kalas, James Manton-Hall, Andreas Orsmond, Mackenzie Shaw and Alex Su (ping @O_S_M if we've missed anyone, guys) They are working together, and the relevant reactions have codes with “SGS” in them.

These guys are making an important synthetic intermediate, shown below right, which can be used in a subsequent reaction to deliver new candidate antimalarials. This is a "divergent" pathway, since we can attach various groups to the Sydney Grammar compound to make a variety of molecules with the same chemistry.

Sydney Grammar School Target

The chemistry’s not easy, but with some precedent this year from Jo Ubels and Tom MacDonald, and inspiration and guidance from Alice Williamson, and expert tuition from their teachers Erin Sheridan and Trent Wallis, they should have a shot at this tricky chemistry. (If you're a student reading this and asking "Can I input?" the answer is "yes" - get in touch)

The route being pursued is nicely shown here, where the first step (SGS 1-1) is also described. The second step (SGS 2-1) was a condensation of a hydrazine with para-CN benzaldehyde, and an attempt was made in parallel using a pyridine aldehyde (SGS 3-1). As this chemistry grows, we're going to need to add it to the synthesis section of the wiki, as a summary of progress.

The chemistry’s not easy - this is certainly more difficult than the stuff that I was doing in high school. Great start, guys - we’re all rooting for you to be able to get to the end of the synthetic sequence! These molecules will be very useful, right now.

 

This post originally authored by Mat Todd


Strings for Google

ClC1=CN=CC(Cl)=N1 InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H LSEAAPGIZCDEEH-UHFFFAOYSA-N

ClC1=CN=CC2=NN=C([Ar])N21 InChI=1S/C5H2ArClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H JTBLVZJIEUOKIG-UHFFFAOYSA-N




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Attached Files
6th November 2014 @ 00:27

The OSM consortium are excited to have some new members to the team; some excellent chemists from Sydney Grammar School. Erin Sheridan and Trent Wallis are working with a group of twelve students to synthesise some building blocks for the Series 4 Triazolopyrazines.

The target compounds were decided following discussion on GitHub and the students are now ready to start on their synthese. Erin and Trent are going to create a separate lab book/blog as part of the consortium's ELN.

There will be more news to follow, hopefully from the students themeselves as they sign up for the ELN, GitHub and Twitter. So watch this space!

There will be prizes awarded to the students who maintain the best ELN, so look out for some great experimental descriptions, photographs, videos and more!

 

GitHub Welcome

Linked Posts