A macrocycle containing two biphenyl and two alanine subunits, synthesis and conformation in solution

2′‐Aminomethylbiphenyl‐2‐carboxylic Acid as Component of a Cyclopeptide; Crystal Structure and Conformation in Solution

“…N-(2'-Phthalimidomethylbiphenyl-2-carbonyl)valine methyl ester 4: A solution of 2 [6] (3.27 g, 9.2 mmol) and H-Val-OMe-HCI (1.53 g, 9.2 mmol) in CH,CI, (50mL) was treated at -10°C. first with 5.5 mL (50 mmol) of N-methylmorpholine (NMM) and then dropwise with 6.2 mL of a SO % solution of propylphosphonic acid anhydride (39 mmol).…”

Antiparallel β‐Sheet Conformation in Cyclopeptides Containing a Pseudo‐amino Acid with a biphenyl moiety

“…We already reported on two cyclic peptides where the pseudo-amino acids 1 (Abc) [4] and 2 (Aba) [5] hold together two valine (Val) or two alanine (Ala) moieties in an antiparallel assembly as in 3.…”

“…This approach did not work in the preparation of the larger compounds 5-8; monomers were isolated under similar conditions. However, the azide cyclization of linear precursors containing two biphenyl and two tripeptide units was successful, giving the 'dimeric' cyclic peptides 5-8 in low to moderate yields The Scheme explains the synthesis: Tripeptide esters were condensed with N-[(tertbutoxy)carbonyl] (Boc) derivatives 9 or 10 of 1 and 2, respectively (prepared from the corresponding N-phthaloyl derivatives) [5], using N-methylmorpholine (NMM) and propylphosphonic anhydride (PPA) [7] to yield the Boc-protected tetrapeptide methyl esters 11-14. The N-terminal Boc group was removed with dioxane/2~ HCl [S] in half of the material of these biphenyl-containing peptides, and the ester group was saponified with 1~ NaOH [9] in the other half.…”

ChemInform Abstract: The Design, Synthesis and Conformation of Some New β‐Hairpin Mimetics: Novel Reagents for Drug and Vaccine Discovery

“…Nevertheless, it is appropriate to highlight the contributions of other groups active in this area. A pioneering contribution was made by Feigel who introduced the phenoxathiin ring system 25,26 , as well as substituted biphenyls 27 , to stabilize b-structure in peptide loops (Figure 3). Related templates were also developed by Müller and Obrecht and coworkers 28 .…”