Synthesis of β³‐Aryl‐Alaninyl Derivatives by sp³ C‐H Activation with Pd(OAc)₂ Catalyst/Pivalic Acid in DCE and Their Structural Studies in Solid State

Abstract

Aryl‐β‐amino acid derivatives are structural constituents of various bioactive natural products, and their peptides have unique folding features for the formation of secondary structure. The substituted β3‐amino acids are mostly prepared from α‐amino acid by Arndt‐Eistert homologation of α‐amino acids, conjugate addition and Mannich reactions synthetic methods. Now sp3 C−H activation is an emerging elegant synthetic method, and employed for the syntheses of various β‐substituted α‐amino acids using Pd(OAc)2 catalyst. This report describes the regioselctive mono arylation of β‐alanine at β3‐postion (adjacent to N‐atom) by sp3 C−H activation methods using Pd(OAc)2 catalyst. Further β3‐phenyl alanine is coupled with α‐(2 S)‐phenyl alanine derivative which produced diasteriomeric hybrid di‐/tri‐peptides. These diastereisomers are purified into optically pure hybrid di‐/tri‐peptides by HPLC. We have explored the role of β3‐phenyl alanine residues in the formation of peptide based supramolecular self‐assembly structures. Hence β3‐aryl alanine and their peptides could be applied for construction of diverse peptidomimics.

Synthesis of R–GABA Derivatives via Pd(II) Catalyzed Enantioselective C(sp3)−H Arylation and Virtual Validation with GABAB1 Receptor for Potential leads

“…Recently, we successfully established a methodology for the regioselective arylation of β-alanine using AQ as a directing group. [25] Since we had working experience with the β-alanine system and GABA being homologue of the β-alanine system, it was curious to know the reactivity of the β-alanine. Further, we anticipated that the result would help the current investigations on deducing the optimisation conditions.…”

“…Similarly, an unsubstituted APAQ L 1 was synthesized for comparison with other ligands (Figure S1). Recently, we successfully established a methodology for the regioselective arylation of β –alanine using AQ as a directing group [25] . Since we had working experience with the β –alanine system and GABA being homologue of the β –alanine system, it was curious to know the reactivity of the β –alanine.…”