Simultaneous Protection and Activation of Amino Acids Using Propargyl Pentafluorophenyl Carbonate

Abstract

[reaction: see text] A very efficient method for the simultaneous protection of the amino group and activation of the carboxyl group of amino acids is reported using propargyl pentafluorophenyl carbonate (PocOPfp). The amino group is protected as a propargyloxycarbonyl (Poc) derivative, and the carboxyl group is activated as a pentafluorophenyl ester. The yields obtained are good to excellent ranging from 60 to 87%.

Activation of hydrocinnamic acids with pentafluorophenol versus pentafluorothiophenol: Reactivity towards hexylamine

“…In summary, four new amides have been synthesised using active esters (PFPE and PFPT) as well as eight intermediate esters and thioesteres (5)(6)(7)(8)(9)(10)(11)(12). It was possible unequivocally conclude that PFPE are the best intermediates for the kind of synthesis and the kind of compounds studied because they gave rise to reactions with less by products, easier work-up, and higher overall yields.…”

“…Subsequent reaction of the active esters (5-8) and thioesters (9)(10)(11)(12) with hexylamine, in chloroform, at room temperature provided the required hexylamides (13-16) (Scheme 2) [17].…”

“…This was the expected result considering the existence of an incomplete reaction when using PFTP as pointed out in the previous discussion. Besides, the usual purification by column chromatography was insufficient to obtain the pure PFPT (9)(10)(11)(12). Therefore, further purification by crystallisation was performed which lead to a dramatic decrease of the yield due to product degradation during this process.…”

“…A commonly used active ester is the pentafluorophenyl ester (PFPE) [3][4][5][6][7][8], which is usually prepared from the reaction of a carboxylic acid with pentafluorophenol using a diimide, such as dicyclohexylcarbodiimide (DCC), as a coupling agent [3,4,7]. A valuable application of PFPE is in the peptide synthesis [3][4][5][9][10][11][12]. These active esters are relatively non-polar, stable to chromatographic purification and extended storage [4,9].…”

Peptide Synthesis

“…The O-propargyl-O 0 -pentafluorophenyl carbonate approach [345] is a different example of the simultaneous N a -protection and carboxy group activation concept. The reaction of O-propargyl-O 0 -pentafluorophenyl carbonate with amino acids brings about Poc-protection (propargyloxycarbonyl-protection) of the N a -group with intermediate formation of a mixed anhydride that readily forms the pentafluorophenyl ester in a one-pot reaction.…”