The Synaptic Leap

The following compounds have been identified as potential antimalarial drugs by GSK-Tres Cantos.

The top compound, known hereafter as 'compound 3', can be found on ChEMBL and ChemSpider:
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL535225 - ChEMBL
https://www.chemspider.com/Chemical-Structure.15995932.html?rid=1e70c7d6... - ChemSpider
 
As can the bottom compound, known hereafter as 'compound 4':

I've been working for six weeks now with the Todd Research Group at Sydney University as part of an undergraduate summer research program. The aim of my project is to synthesise analogues of this group of hits from the  antimalarial dataset released by GSK. They are referred to here as 'near neighbours' because they share the arylpyrrole moiety present in the two hits (TCMDC 123812 and 123794) Paul has been working on, but have a thiazolodinone side chain. The major components of my project are:

We have received encouraging biological results for the analogues we sent for testing before Christmas. Mat has discussed this here on TSL and on G+. Our best hit came from the "near-neighbour" compound and the original GSK hits came out slightly less active than in their original high throughput screen. However, Paul Willis at MMV rates TCMDC-123794 as a better lead than PMY 14-1 (TSL post).

I was looking at all the difficulty that is occuring with finding a cheap source of chiral catalyst for the Pictet-Splenger and mused about using Phenylglycine, as this avoids the issue due to it being part of the chiral pool.
Anyway here is my attempt at getting the key ring system together for the system. Don't think anything I used is particularly expensive. Sorry about the conditions being vague, was just a quick thought that I came up with.

Background
Relevant experiment.  Basically, the Pictet-Spengler to form 3 PZQ analogues and PZQ itself.
The mass spec is of a by-product of the acid mediated PS cyclisation of MNR10-1 to form KAB8-1, aka the dimethoxy N-benzoyl PZQ analogue.

 I have just packaged up TCMDC-123794 (PMY 11-2) and -123812 (PMY 10-2) along with the parent acid (PMY 8-2), ester (PMY 6-1), aldehyde (PMY 2-4), near neighbour analogue (PMY 14-1) and also the acylurea by-product (PMY 12-1-A). These have been sent to GSK Tres Cantos where the original study was carried out for further testing.

I'm now happy with the data for TCMDC-123812 and TCMDC-123794. A bit of usual practical annoynce with TCMDC-123794 caused some trivial issues, namely a bit of repurification and acetone in the final spectra. These have now been taken care of and the compounds are ready for testing!
I've summarised the various intermediates and other compounds that are in the works on OpenWetWare. Please get in touch if you're interested in testing them.

I'm now fairly confident that I've made TCMDC-123794 and TCMDC-123812. By fairly confident I mean that I've got a reasonable looking but crude 1H NMR and low res. mass spec of both of the compounds. They are not clean by NMR after a column and the yield of the reaction was pretty bad (~20%). Still this isn't too bad for a first go, using a quick and dirty acid chloride. Most of the mass seems to go toward turning the acid into the anhydride. This is supported by NMR but mass spec hasn't given a positive result so far.