Synthesis of β-hexa- and β-heptapeptides containing novel β 2,3-amino acids with two serine or two cysteine side chains - CD- and NMR-spectroscopic evidence for 3 14-helical secondary structures in water

Dieter Seebach*, Albrecht Jacobi, Magnus Rueping, Karl Gademann, Martin Ernst, Bernhard Jaun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Two representatives of a new type of β-amino acids, carrying two functionalized side chains, one in the 2- and one in the 3-position, have been prepared stereoselectively: a β-Ser derivative with an additional CH 2OH group in the 2-position (for β-peptides with better water solubility; Scheme 2) and a β-HCys derivative with an additional CH 2SBn group in the 2-position (for disulfide formation and metal complexation with the derived β-peptides; Scheme 3). Also, a simple method for the preparation of α-methylidene-β-amino acids is presented (see Boc-2-methylidene-β-HLeu-OH, 8 in Scheme 3). The two amino acids with two serine or two cysteine side chains are incorporated into a β-hexa- and two β-heptapeptides (18 and 23/24, resp.), which carry up to four CH 2OH groups. Disulfide formation with the β-peptides carrying two CH 2SH groups generates very stable 1,2-dithiane rings in the centre of the β-heptapeptides, and a cyclohexane analog was also prepared (cf. 27 in Scheme 6). The CD spectra in H 2O clearly indicate the presence of 3 14-helical structures of those β-peptides (18, 23, 24, 27b) having the 'right' configurations at all stereogenic centers (Fig. 2). NMR Measurements (Tables 1 and 2, and Fig. 4) in aqueous solution of one of the new β-peptides (24) are interpreted on the assumption that the predominant secondary structure is the 3 14-helix, a conformation that has been found to be typical for β-peptides in MeOH or pyridine solution, according to our previous NMR investigations.

Original languageEnglish (US)
Pages (from-to)2115-2140
Number of pages26
JournalHelvetica Chimica Acta
Volume83
Issue number9
DOIs
StatePublished - Oct 31 2000

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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