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BOSS XI… Or What I Did On My Summer Holidays   

19 July 2008 9,407 views 11 Comments

I’m still ‘out of the office’ just now – on holiday with my family back in Embra (Edinburgh to non-natives), but the conference ended yesterday, so I thought I’d write a bit about what was discussed.  The gist of the conference was five days of organic synthesis – and only one lecture theatre, so no timetabling issues.  The lectures were also all scheduled to last the same 60 minutes – which I’m surprised to say was mostly adhered to.  No random Sharpless 2h+ ramblings…

Day 1.  (Carreira Day)

A tradition of the conference is that the first day is dedicated entirely to the recipient of the Tetrahedron Chair – and this year it was the turn of Erick Carreira.  The award it’s self compromises a fat pile of cash, along with the lecture floor for the day – in this case four lectures totalling nearly five hours of chemistry.

1. First-up was a discussion about amphotericin B, which was blogged here back in may.  The deal was that by cutting-out the C-35 hydroxyl, one might prevent the molecule from allowing ion efflux from cell membranes, and thereby understand how the natural product’s activity originated.

2. A quick break and then it was time to med-chem our arses – with a bit of oxetane synthesis and analysis.

These little bad-boys have been developed by Carreira as alternatives to cyclopropanes or gem-dimethyl groups for use in drug targets.  They block sites (like benzylic positions) that are prone to fast metabolism, but unlike the latter, oxetanes aren’t lipophillic, and actually appear to lower the logP (an increase in polarity).  But to get used, they’ve got to be easy to procure:

First was the synthesis of the key substrate for bolting-on the oxetanes – Oxetan-3-one.  Two older syntheses were mentioned – both rather laborious – with a new one developed by the man.

Bolting this group onto molecules involved two main routes – direct addition of an organometallic to the ketone and then functionalisation of the resulting hydroxyl (or reduction).  The other method was olefination (Wittig), and then transformation of the alkene by hydrometalation and cross-couplling.

3.  Next up was a more traditional methodology lecture – in this case with a bias towards nitro-alkenes, and their asymmetric hydrogenation to give chiral nitro-compounds.

Then a bit of asymmetric hydroboration:

This has been done before, but using Brown’s QUINAP ligand, which is more difficult to procure than Carreira’s PINAP.  He also used the PINAP ligand to provide asymmetry in conjugate addition of acetylenes:

There was also quite a bit of stuff on cobalt catalysed functionalisation of olefins – hydroazidation, hydrocyanation and hydrochlorination:

Last was an example of this type of chemistry in synthesis, with the completion of Strychnofoline.  We covered this beastie back in 2006 – the early days of this website!

More shortly…

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11 Comments

  • anniechem says:

    I can’t wait to read more! I’m so jealous that you were at BOSS….the lineup was pretty impressive.

  • TWYI says:

    Sure to be better than the absolute joke that was ICOS-17

  • anniechem says:

    ok, TWYI, you’ve piqued my interest….why was ICOS-17 an “absolute joke”? Please elaborate!

  • DaveB says:

    Hi! Great report, amazing stuff and as usual you have no equal to summarize chemistry with just enough words to make it stunning! Congrats. Just a very minor typo: your second scheme seems to be missing a ketal protection at the end of the first step. Or maybe I misunderstood sth…
    Greetings, Dave

  • ryan says:

    i almost cannot understand so complex methods can use in practical synthesis6^^^^^^^^^^^^^^

  • ZAL says:

    Didn’t Carreira mention that the Co-catalyzed hydroazidation works with safrole too (hence its great economic relevance…)? I seem to remember that it was in one of his papers. I may need Milkshake help here, if I am not wrong he commented about that on his blog.

  • [...] and Trost. I’m not going into detail about the lectures, as this seems to be covered in Tot. Synth. You can see the full programme [...]

  • MCC says:

    What is K-10 clay??

  • Pilky01 says:

    Its effectively a heterogenous acid source

  • milkshake says:

    also, activated molecular sieves tend to be mildly acidic – with super-sensitive things like enol ethers one earns a suprise rather easily….

  • Alexey says:

    To Milkshake:
    do you or your colleagues actually use oxetane moiety in med chem? This stuff is alread ca. 2 yeras (?) old, may you know some up-to-date roomers about it? Carreira presented it quite good, but he didn’t say that it gave some real results.