They let me out of the lab today. It was time for the annual Synthetic Symposium that was held at Flinders University this year. As usual they fly two big wigs in to present stuff. The remaining talks (6 this time) is given by PhD students. This year the big wigs were Professor Martin Banwell from the Australian National University and Professor Mukund Sibi from North Dakota State University. Both of them gave very interesting talks indeed. Apparently what these guys do is old news. Well It was news to me so here's a brief crackdown on what Banwell had to say. Banwell is a total synthesis man and today he was talking about the synthesis of compounds such as Brunsvigine, Complicatic Acid, 11-O-Debenzoyltashironine etc. The talk was entitled "Chemoenzymatic Methods in Synthesis" and it was the whole chemoenzymatic bit that caught my attention. Basically they are taking simple substituted benzenes and dihydroxylating them. Truly amazing stuff:
As Banwell pointed out the example with styrene is unbelievable and the ee's are through the roof! Moreover, the concept isn't limited to monosubstituted systems and more than 250 metabolites of this kind are known by now. So a couple of things immediately spring to mind. What scale can you do this sort of thing on and how do you get the other enantiomer of your product if that is what you are after. Well Banwell was on top of things and addressed these matters during his talk. Firstly, this stuff can be done on big scale. In the case of bromo- and chlorobenzene they obtain 35 grams of stuff per litre of fermentation broth which is pretty damn impressive. If you want the other enantiomer things are a bit trickier. However, Allen et al. have developed a method where the enantioselectivity is switched by introducing an iodine substituent that can be removed after the dihydroxylation:
A nice and simple solution to a complex problem that was published in Chemical Communications in 1995 (DOI: 10.1039/C39950000117). Anyway, this was just Banwell's introduction. He went on to talk about the total synthesis of a whole range of natural products starting from these metabolites. Most of it was unpublished stuff so I'll be a good boy and not post it all here just yet. Enough for now. I'll post what Professor Sibi had to say some other day. D!
As Banwell pointed out the example with styrene is unbelievable and the ee's are through the roof! Moreover, the concept isn't limited to monosubstituted systems and more than 250 metabolites of this kind are known by now. So a couple of things immediately spring to mind. What scale can you do this sort of thing on and how do you get the other enantiomer of your product if that is what you are after. Well Banwell was on top of things and addressed these matters during his talk. Firstly, this stuff can be done on big scale. In the case of bromo- and chlorobenzene they obtain 35 grams of stuff per litre of fermentation broth which is pretty damn impressive. If you want the other enantiomer things are a bit trickier. However, Allen et al. have developed a method where the enantioselectivity is switched by introducing an iodine substituent that can be removed after the dihydroxylation:A nice and simple solution to a complex problem that was published in Chemical Communications in 1995 (DOI: 10.1039/C39950000117). Anyway, this was just Banwell's introduction. He went on to talk about the total synthesis of a whole range of natural products starting from these metabolites. Most of it was unpublished stuff so I'll be a good boy and not post it all here just yet. Enough for now. I'll post what Professor Sibi had to say some other day. D!
Andy Myers used a similar dihydroxylation reaction at the beginning of his syntheses of the tetracyclines (Science 2005, 308, 395 and JACS 2005, 127, 10323). I don't precisely recall the scale they ran the reaction on, but it was massive. I saw pictures of the reactor they used and it took up probably half of a fume hood.
ReplyDeleteThere's a picture of the bioreactor that the Banwell group uses on Banwell's personal webpage: http://rsc.anu.edu.au/~mgb/
ReplyDeleteLooks pretty sophisticated. Is this sort of gear really necessary or is it possible to do this sort of thing using simple cheap equipment. The beast the Banwell group is showing off looks pretty expensive. D!
Tomas Hudlicky (Brock) also runs these dihydroxylations. I seem to recall either him or Andy Myers saying they were using cheap carboys you use for making homemade wine as the apparatus.
ReplyDeleteMust have been Myers, Hudlicky was my old boss and does the biooxid. on larger scale. bromo diene diols are primary sm for group, at least as of a couple years ago
ReplyDelete