Configurational and conformational control on formation and oligomerization of 2-C mono-arylated pseudo-proline dipeptide building units by aromatic stacking interactions

Electrophilically induced cyclic acetal formation of the O-benzyl dipeptide esters Fmoc-NMeIle-Thr-OBn (1) and of Fmoc-Pro-Thr-OBn (6) has been observ ed to lead predominantly to the (R) diastereomers 2b and 8b at the 2-C posi tion of the resulting substituted Id-oxazolidine (Psi Pro) unit, while upon acetalization of the corresponding O-methyl ester 4 the 2-C(S) epimer 5a i s predominantly formed under the same proton catalyzed cyclization conditio ns. With boron trifluoride etherate as Lewis acid the reaction is particula rly fast and leads selectively to the prolyl threonine derived 2-C(R) dipep tide building block 8b, which could conveniently be assembled into a noname r with a virtually solvent independent CD-spectrum of the polyproline type I (cis amide bonds).