A Novel Synthesis of Chiral Guanidinium Receptors and Their Use in Unfolding the Energetics of Enantiorecognition of Chiral Carboxylates

Abstract

A novel synthetic route to the versatile chiral bicyclic guanidinium building block is described making use of l-methionine as a starting material from the natural chiral pool. Furthermore, the synthetic elaboration of this building block is shown in the construction of macrocyclic and open chain hosts, respectively. The host design employs urea functions as the connecting units and supplementary anchor groups for the complexation of anions. The binding studies of these hosts with various chiral and achiral oxoanions are performed by isothermal titration calorimetry. A trend analysis of the binding energetics in an ensemble of structurally similar guests discloses the importance of geometrical confinement of the guest. Association entropy rather than free energy (affinity) is identified as an indicator of structural uniqueness needed to distinguish configurational isomers in the recognition of enantiomeric carboxylates by the chiral guanidinium hosts.

Photochemically Stable Fluorescent Heteroditopic Ligands for Zinc Ion

“…[63][64][65][66][67][68][69] However, the examples of using ITC in studying metal-ligand coordination in organic solVents are rare, 70,71 partly because ∆G°of metal coordination in organic solvents is usually larger than what may be accurately measured by ITC. However, we note that the ∆H°and n values can still be reliably determined from ITC experiments.…”

A new water soluble Zn‐salophen derivative as a receptor for α‐aminoacids: Unexpected chiral discrimination

“…This finding suggests that some kind of interaction should take place between the receptor and the phenyl ring of the bound substrate, thus introducing a third point of contact, 5 even if a role of entropies is also to be considered as a possible explanation. 27 Although PM3 calculations in the gas phase did not give any indication on the nature of such an interaction, we believe that p. . .p stacking with one of the salophen aromatic rings or OÀ ÀH.…”

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

“…Previous syntheses of bicylic guanidines 2 and 6 – 9 started from enantiomerically pure α-amino acids [6,8,10,16–17] or from their reduction products, chiral α-amino alcohols [9,18]. In contrast, our approach used the racemic ester rac- 12 of β-phenylalanine, easily accessible in a Knoevenagel-type condensation of benzaldehyde 11 , ammonium acetate and malonic acid, followed by esterification (Scheme 1) [20–21].…”