The first synthesis of a tricyclic homodetic peptide employing coordinated orthogonal protection

Abstract

In an effort to cause significant conformational distortion and thereby possibly generate a pure SRIF antagonist, we undertook the synthesis of 2, the first homodetic tricyclic peptide. This required five dimensional orthogonal amino protection and three carboxyl protecting groups to allow the selective closure of the three rings and to differentiate the ε-amino groups of the two lysines. We also exploited acid catalyzed removal from the resin to achieve selective deprotection of a side chain carboxyl moiety simultaneously with its partner amino group for subsequent cyclization.