Latest piece for the RSC in the May issue of Chemistry World
Fantastic work. A formidable solution to a long standing problem, i.e. construction of epidithiodiketopiperazine core, specifically the disulfide bridge. ~ A+
Very nice tetrahydroxylation and clever way to incorporate sulfur diastereoselectively.
Just reading in about Seebach’s self chirality which was referred to by this paper. I really like this guy, new on the block but very promising. The tetra steps are bloody nice. Great paper.
I’m not a huge total synthesis fan but hats off to Movassaghi.
where did this guy come from? he has pretty good pedigree but average publication track record. and out of now where, he pulls this little trick out of his hat. i guess it just goes to show that publication track record isn’t the be all end all for a budding career.
one comment: based on his methodology to generate the bispyrroloindoline segment of this molecule. he really only had a couple approaches available to him to install the disulfide linkages: bring them in preformed or put them in at the end. i think the approach is impressive in execution, but really its not too surprising.
Saw him talk on this at the ACS- he said in addition to the disulfides, one of the main issues was *horrific* NMR spectra. They don’t look as terrible in the SI as I had expected, however.
Hah, I looked at this target and said to myself, “I totally think you could use Movassaghi’s radical dimerization technique to make this thing”. Lo and behold, it’s a Movassaghi paper! Way to get the most bang for your buck on this methodology.
Reminds me of silver hydroxylation in axinellamine.
This reminds me of Kapakahines, yet its in RSC…. Go figure. I’m actually impressed by the tetrahydroxylation, since I would have guessed the aminals would have also oxidized under these conditions to create an “orthoformate-like” species. Any ideas on why this doesn’t happen? Tosylamides can be oxidized (i.e Kolbe) under similar conditions to amides, so why the selectivity? I can’t see why a radical pathway would favor the amides and not the aminal. Anyone know why? Any precedent?
The diketopiperazine C-H bonds are weaker than the aminal C-H bonds due to captodative stabilization. Radicals adjacent to both electron withdrawing groups (EWGs) and electron donating groups (EDGs) are more stable than radicals adjacent to only EGDs or EWGs. Hence, homolytic cleavage of the diketopiperazine C-H bonds to generate intermediate captodative radicals is faster than cleavage of aminal C-H bonds.
sorry misread that. its in science. i’m confused.
I was too centered on the reactivity of the amide and didn’t consider the effect of the carbonyl also attached to the carbon. That makes sense.
Are we through another slump in the # of Total Syntheses? or am i missing some abstracts?
Nice job! BTW, does anybody know a little more about this guy? Heard that he’s pretty tough