Induced Axial Chirality in the Biphenyl Core of the Proatropoisomeric, C^α‐Tetrasubstituted α‐Amino Acid Residue Bip in Peptides

Abstract

An induced axial chirality in the biphenyl core of the 2',1':1,2;1'',2'':3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid (Bip) residue, a conformationally labile, atropoisomeric, C(alpha)-tetrasubstituted alpha-amino acid, was observed by CD and (1)H NMR spectroscopic techniques in the linear dipeptides Boc-Bip-Xaa*-OMe where Boc=tert-butoxycarbonyl, OMe=methoxy, and Xaa*=D- and/or L-Ala, -Val, -Leu, -Phe, -(alphaMe)Val and -(alphaMe)Leu. Chiral induction was significantly lower in the isomeric dipeptides Boc-Xaa*-Bip-OMe, with the Xaa* residue located at the N-terminus of Bip, as well as in the cyclic dipeptide cyclo-[Bip-L-Ala]. The results obtained in solution were confirmed by X-ray diffraction analysis of a crystalline sample of Boc-(R)-Bip-D-Ala-OMe.

Helical screw‐sense preferences of peptides based on chiral, Cα‐tetrasubstituted α‐amino acids

“…Peptides based on Bin and Bip show a clear tendency for β‐turn and 3 10 ‐helical structures, although in short peptides the fully extended conformation would also be populated to some extent.…”

“…A relationship between axial chirality, side‐chain torsion angles and helical screw‐sense identical to that of Bin can be derived from the crystal structures of Bip peptides and derivatives, in which ( S )‐Bip is always left‐handed helical and ( R )‐Bip right‐handed helical. In solution, however, at variance with Bin, the ( S ) and ( R ) enantiomers of Bip can interconvert.…”

“…More specifically, C‐terminal L ‐ and D ‐ amino acid residues preferentially induce in the preceding Bip residue ( S ) and ( R ) axial chiralities, respectively, which can be determined by the sign (negative and positive, respectively) of the CD signal at 250 nm. On this basis, Bip can be exploited as a tool for the configurational assignment of chiral amino acids, amines, and alcohols …”

Tropos Amino Alcohol Mediated Enantioselective Aryl Transfer Reactions to Aromatic Aldehydes

“…[1] Usually, such atropisomeric systems are required to be configurationally stable at the reaction temperature because configurationally flexible biaryls undergo rapid racemization, which makes them unable to transfer any chiral information. The latter approach shows a more general character, and it has been applied as both a method of chirality detection, developing flexible biphenyl probes for absolute configuration assignment via electronic circular dichroism (ECD) spectroscopy, [3,4] and as a source of chirality induction, allowing numerous efficient chiral ligands that are employed in asymmetric catalysis devel-oped. Such central-to axial-chirality transfer can occur through both noncovalent and covalent interactions.…”

Enantioselective sensing of chiral amino alcohols with a stereodynamic arylacetylene‐based probe

“…The development of conformationally flexible receptors capable of reporting a molecular recognition event upon binding to a substrate provides new avenues for chiroptical analysis . For example, Rosini and Toniolo demonstrated that the absolute configuration of chiral amino acids, carboxylic acids, and alcohols can be correlated to the ICD output of a covalently linked stereodynamic biphenyl reporter unit . The same principles have been exploited with molecular bevel gears, propellers, and other well‐defined arrangements .…”