Hydrogen-Bonding Donor/Acceptor Scales in -Sulfonamidopeptides

Abstract

The conformational preferences of b-sulfonamidopeptides in chloroform solution were investigated by variable-temperature 1 H NMR spectroscopy and FT-IR spectroscopy. The following hydrogen-bonding acceptor scale was derived from the experiments: RCON % tBuOCON b COOMe ! RS-O 2 N. An intermolecular study gave results complementary to those described above: the N ± H stretch bands of Nmethylacetamide and N-methyl methanesulfonamide in chloroform were followed during titration with excess methanesulfonylpyrrolidine and N,N-dimethylacetamide.Shifts to lower frequencies were observed which are correlated with the hydrogen-bond strengths and show that the amide is a stronger hydrogen-bond acceptor than the sulfonamide.

Conformational Analysis of Azabicycloalkane Amino Acid Scaffolds as Reverse-Turn Inducer Dipeptide Mimics

“…On the basis of model compounds, [16] these are known to give rise to three distinct absorbances, at 1680Ϫ1675 cm Ϫ1 for the free secondary amide, at 1665 cm Ϫ1 for the free tertiary amide of the 6,5-fused bicyclic lactam, and at 1730 cm Ϫ1 for the free carbamate. Hydrogen bonding to the carbonyl shifts the band at lower frequency by 20Ϫ30 cm Ϫ1 .…”

Synthesis, Conformational Studies and Binding Properties of Acyclic Receptors for N-Protected Amino Acids and Dipeptides

“…The unchanged amino groups on the resin were capped with acetylimidazole (AcIm). Deprotection of the Fmoc groups and treatment with the -valine-derived β-NFmoc-aminosulfonyl chloride 8, with DMAP as catalyst and methyl trimethylsilyl dimethylketene acetal (MTDA) as HCl scavenger, [14,17] gave the bis(sulfonamide) 10. Two cycles were required to ensure completion of the coupling, until no free amino groups could be detected by two different colour tests.…”

“…[19] At a concentration of 8.5 m in CDCl 3 , the signal of the amidopyridine NH 1 protons appeared at unexpectedly low field (δ ϭ 9.41, see Table 1, standard values δ ϭ 8.00Ϫ8.50 [1b][10a] ), whilst the sulfonamide protons NH 2 were also strongly deshielded (δ ϭ 6.32 compared to their standard values δ ϭ 4.50Ϫ4.74). [14] The acetamide NH 3 proton signals were located closer to their traditional chemical shifts (δ ϭ 6.22 compared to 6.00Ϫ6.20).…”

“…[1b,10] Recently, an interest in synthetic receptors based on peptidosulfonamide sidearms has also emerged. [3,11Ϫ13] Over the past five years, the group in Milano has been studying the conformational preferences of unnatural biopolymer scaffolds containing β-sulfonamidopeptides [14] and vinylogous sulfonamidopeptides. [15] Sulfonamidopeptides display an aspect of the covalent framework that is essential for the formation of folded structures by intramolecular hydrogen bonding: The repeating backbone structure contains both hydrogen-bond donors (strong: CONH; very strong: SO 2 NH) and hydrogen-bond acceptors (strong: CϭO; weak: SO 2 N).…”

“…[15] Sulfonamidopeptides display an aspect of the covalent framework that is essential for the formation of folded structures by intramolecular hydrogen bonding: The repeating backbone structure contains both hydrogen-bond donors (strong: CONH; very strong: SO 2 NH) and hydrogen-bond acceptors (strong: CϭO; weak: SO 2 N). [14,15] In this paper we report the synthesis and conformational and binding studies of a novel class of ''two-armed'' synthetic receptors for N-protected amino acids and dipeptides, each containing a 2,6-diamidopyridine binding unit bearing pendant pseudo-peptide legs consisting of an amino acid (-Phe) and chiral β-aminosulfonamides. [16] One of these receptors in particular (5, Figure 1) displays a high binding selectivity for the dipeptide N-Cbz--Ala--AlaOH (Cbz ϭ benzyloxycarbonyl) over its enantiomer N-Cbz--Ala--AlaOH.…”