Amino acid chemistry is not my favorite; it's kind of... blah. Feels archaic somehow. But these amino acids are pretty funky - each fragment was formed with pretty standard chemistry (protections/deprotections and all). The N-N bonds were introduced with benzyl carbazate and t-butyl carbazate. The cyclization to form the leftmost-indicated piperazic ring occurred via Mitsunobu condition-induced Fmoc deprotection of the amine (which appears to be novel according to the article) followed by substitution of an alcohol, while the left occurred via Boc deprotection-induced displacement of a triflate and the top via Troc-deprotection induced displacement of a triflate. Don't forget the structures of these (the deprotection conditions used in the paper alongside):
The most interesting part is the macrocyclization; rather than doing a macrolactonization between an acid or ester and an alcohol, the authors used a substitutive strategy by a carboxylate anion attacking a chlorine-turned-iodide leaving group to produce Piperazimycin A in 3.6% overall yield in 26 linear steps. Tight. Note the hexachloroacetone (HCA) used for chlorination in the Appel reaction instead of CCl4. Equally toxic reagent, but way cooler. Monday, October 26, 2009
Piperazimycin A: A Cyctotoxic Cyclic Hexadepsipetide
Li, Gan, and Ma's recent natural product synthesis of piperazimycin A, the structure of which was reported in 2007, in Angewante Chemie (doi: 10.1002/anie.200904603), attracted me admittedly because of how gorgeous the 18-membered ring with 6 carbonyls pointed toward each other is - seriously, look at it! Stare into the center of the ring - the oxygens are sort of mesmerizing in a hypnotic sort of way, no?
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This is really interesting because it reminded me when I was in the high school, now this is interesting because I understand everything I'd like to get a little bit more information , thanks for it.
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