Straightforward synthesis of cholic acid stabilized loop mimetics

We here report on a new straightforward strategy for the synthesis of cyclic cholic acid–peptide conjugates. A solid-phase synthesis method is presented in which a selected anti-lysozyme CDR3 fragment, Asp-Ser-Thr-Ile-Tyr-Ala-Ser-Tyr-Tyr-Glu-Ser, is immobilized onto a steroidal cholic acid derived scaffold in order to yield a loop-like structure. Therefore, part of the desired sequence, that is, Ser-Tyr-Tyr-Glu-Ser, is introduced, at the C12 position of the scaffold. Subsequently, the remainder of the envisaged sequence is introduced at C3 via a Cu-catalyzed cyclo-addition reaction. Finally, amide bond formation delivers the desired cyclic peptidosteroid. This new synthetic strategy offers an easy and short access to cyclic peptidosteroids via convergent peptide ligation and macrocyclization.