N-terminus to C-terminus metallacyclicpeptides employing tungsten–alkyne coordination

The capacity of using tungsten–alkyne coordination to form metallacyclicpeptides was examined. Dialkynyl species 1, 2 and 3 were prepared. 1 is a dialkyne derivative of ammonia, 2 is a dialkyne derivative of alanine, while 3 is a dialkyne derivative of the dipeptide alanylalanine. In 2 and 3 the two alkyne groups were appended at the N- and C-termini. The N-terminal alkyne was prepared by acylating the N-terminal amine with propargylchloroformate. The C-terminal alkyne was introduced by acylating the C-terminal carboxylic acid with propargylamine. Outcomes of metallacyclization reactions were assessed using 1H NMR spectroscopy and electrospray positive ion mass spectrometry. Both 2 and 3 underwent successful cyclization to yield the metallacyclicpeptides 16 and 17, respectively. However, 1 did not cyclize; instead, it formed a variety of acyclic and cyclic oligomeric tungsten–bis(alkyne) species. The failure of 1 to cyclize is attributed to its inability to position its two alkyne groups parallel to each other and spaced 6.5 Å apart. The 1H NMR spectra for 16 and 17 show that these metallacyclicpeptides exist as a complex mixture of isomers that differ in how the ligands are positioned around the tungsten center. At elevated temperatures metallcyclicpeptide 17 will rapidly interconvert between the various isomers. In contrast, 16 does not readily interconvert between isomers, even at elevated temperatures. That 16 does not rapidly interconvert between isomers, even at 90 °C, is attributed to the tight packing and limited conformational freedom of this metallacyclicpeptide.