Synthesis of β-hexa- and β-heptapeptides containing novel β2,3-amino acids with two serine or two cysteine side chains - CD- and NMR-spectroscopic evidence for 314-helical secondary structures in water

Two representatives of a new type of beta-amino acids, carrying two functionalized side chains, one in the 2- and one in the 3-position, have been prepd. stereoselectively: a beta-Ser deriv. with an addnl. CH2OH group in the 2-position, for beta-peptides with better water soly., and a beta-HCys deriv. with an addnl. CH2SBn group in the 2-position, for disulfide formation and metal complexation with the derived beta-peptides. Also, a simple method for the prepn. of alpha-methylidene-beta-amino acids is presented. The two amino acids with two serine or two cysteine side chains are incorporated into a beta-hexa- and two beta-heptapeptides, which carry up to four CH2OH groups. Disulfide formation with the beta-peptides carrying two CH2SH groups generates very stable 1,2-dithiane rings in the center of the beta-heptapeptides, and a cyclohexane analog was also prepd. The CD spectra in H2O clearly indicate the presence of 314-helical structures of those beta-peptides having the "right" configurations at all stereogenic centers. NMR measurements in aq. soln. of one of the new beta-peptides are interpreted on the assumption that the predominant secondary structure is the 314-helix, a conformation that has been found to be typical for beta-peptides in MeOH or pyridine soln., according to our previous NMR investigations. [on SciFinder (R)]