Linear and cyclic beta(3)-oligopeptides with functionalised side-chains (-CH2OBn, -CO2Bn, -CH(2)CH(2)CO2Bn) derived from serine and from aspartic and glutamic acid

摘要

The natural beta-amino acid derivative Boc-Asp(beta-OH)-OBn, as well as Boc-beta-HGlu(OBn)-OH and Boc-beta-HSer(OBn)-OH (prepared from appropriately protected glutamic acid and serine, respectively, by Arndt-Eistert homologation), were employed as building blocks for the synthesis of linear (11-20) and cyclic (21-23) beta-oligopeptides consisting of two to six beta beta-amino acids [using trichloroethyl (TCE) ester groups for C-terminal protection and pentafluorophenyl-ester activation for macrocyclisation]. While the linear derivatives are soluble enough for reactions and structural investigations in solution, the cyclo-beta-tri- and -hexapeptides are not (according to FT-IR measurements they form networks of hydrogen bonds, perhaps consisting of so-called nanotubes). The CD spectra of the Boc-OTCE-protected (19) and of the unprotected (20) beta-hexapeptides [beta-Asp(OBn)-beta-HGlu(OBn)-beta-HSer(OBn)](2) differ drastically, and only the unprotected form shows the familiar pattern of a negative Cotton effect between 210 and 220 nm (indicative of a 3(14) helix). An NMR analysis in methanol of the beta-hexapeptide 20 with free termini reveals the presence of a single, central, left-handed helix turn (14-membered hydrogen-bonded ring). The results are discussed and compared with those obtained previously for analogous beta-peptides carrying non-functionalised side chains. [References: 43]