Totally Synthetic by Paul H. Docherty, 21 September 2006
Total Synthesis of Bengazole
J. A. Bull, E. P. Balskus, R. A. J. Horan, M. Langner, S. V. Ley, Angew. Chem. Int. Ed. 2006, 45, 6714-6718.
A sweet and ultimately short total synthesis of this interesting target. I won’t bore you with a list of biological activity - suffice to say that it’s a very potent anti-fungal agent, and also anthelmintic. Their strategy was based around a unifying and diastereoselective [3+2] nitrile oxide cyclisation. This was used to impart the stereochemistry on one of the “down” via the inside alkoxy effect. The other could then be derived from the reduction of a ketone with Et2BOMe.
This is a thoroughly creative method of generating a 1,3-diol in a stereochemically defined manner, and is well exemplified in this synthesis. They also show two methods of generating an oxazole, one from an amide/aldehyde intramolecular cyclisation which I found particularly interesting.
It’s used to chlorinate the oxime; they then eliminate with the base and make the nitrile oxide, which is the reactive species for the [3+2]
NCS gives you a chloro-oxime: R-CH=N-OH -> R-CCl=N-OH, which then breaks to nitrile oxide R-N(+)#O(-) which is of course the actual compound reacting with the double bond. # stands for a triple bond.
Somebody correct if I lied too much
And by the way I like this synthesis.
What does the NCS do in the first step?