9] Solid-phase synthesis of cyclic homodetic peptides

Abstract

This chapter discusses solid-phase synthesis of cyclic homodetic peptides. It reviews the synthesis of cyclic homodetic peptides by solid-phase methods with an emphasis on solid supports, protecting group strategy, reagents, side reactions, and the emergence of cyclic peptide combinatorial libraries. There are two general classes of cyclic peptides: (1) homodetic and (2) heterodetic. Ring formation may occur to form the amide linkage between an amino and carboxylic acid function to give homodetic cyclic peptides, whereas any other linkages such as lactone, ether, thioether, and, most commonly, the disulfide bridge are referred to as heterodetic. Cyclic hexapeptides containing a proline to further restrict conformational possibilities were prepared and extensively studied. With the development of improved synthetic methods, larger ring sizes and more intriguing targets have been successfully attempted.