Auxiliary mediated synthesis of ring-strained lactams

by J.P.A. Rutters

Institution: Universiteit van Amsterdam
Year: 2015
Record ID: 1242488
Full text PDF: http://hdl.handle.net/11245/1.437846


Small and strained lactams (pentapeptides, tetrapeptides or seven-membered bislactams) are a naturally abundant but synthetically elusive class of compounds. These cyclic peptides are used in varying fields such as material sciences or as organic catalysts. The main use of small cyclic peptides, however, can be found in pharmaceutical research. Their rigid structure often enhances biological receptor binding. Due to ring strain, 7-15 membered cyclic peptides are extremely difficult to synthesise. The research in this thesis has been directed towards the design of auxiliaries in an effort to develop a general method for auxiliary-mediated cyclisation of highly constrained cyclic peptides. Three classes of auxiliaries will be discussed in this Thesis: N-terminal auxiliaries, internal auxiliaries and C-terminal auxiliaries. These auxiliaries mediate cyclisation via initial formation of a larger cyclic intermediate, reducing the strain of the ring and thus facilitating initial cyclisation. Subsequent ring contraction and auxiliary removal yields a cyclic peptide of the desired ring size.