Cyclization of Linear Tetrapeptides Containing N-Methylated Amino Acids by using 1-Propanephosphonic Acid Anhydride

Shengping Zhang, Luis M. De Leon Rodriguez, Ernest Lacey, Andrew M. Piggott, Ivanhoe K. H. Leung, Margaret A. Brimble

Europ. JOC, 2017, 149.

Publication Date: November 7, 2016


The synthesis of a series of naturally occurring cyclotetrapeptides and an analogue with 1-propanephosphonic acid anhydride (T3P) is reported. An unexpected finding is the formation of unstable cyclic peptide conformers in addition to the more stable trans,cis,trans,cis (tctc) cyclopeptides.

The cyclization of the linear tetrapeptides sequence H-NMePhe-Xaa1NMePhe-Xaa2-OH (for which Xaa1 = Xaa2 = Ile, Val, or Leu; Xaa1 = Val; Xaa2 = Ile or Leu) by using 1-propanephosphonic acid anhydride was explored. An unanticipated finding is the cyclization towards cyclotetrapeptide conformers (kinetic products) that were highly prone to hydrolysis and that slowly interconvert into the more stable trans,cis,trans,cis (tctc) conformers (thermodynamic products).

Contact Us

Business Development

Microbial Diversity

Metabolic & Chemical Diversity




Stay in the loop

Recent publications