Novel Enantioselective Receptors for N‐Protected Glutamate and Aspartate

Abstract

A series of chiral bisthiourea macrocycles 1-4 have been prepared and their binding properties with various dicarboxylate salts have been examined by using NMR titration and isothermal calorimetry experiments. Macrocycle 1, in particular, favours the 1:1 binding of N-protected L-glutamate and aspartate, but favours 1:2 binding of the corresponding D-amino acids in polar solvents (dimethyl sulfoxide and acetonitrile). The macrocycles, however, do not bind carboxylates at all in the less competitive solvent chloroform. The binding properties of these macrocyles are sensitive to small structural changes as demonstrated by the altered binding properties of macrocycles 2-4 compared with 1.

A Combined Computational and Experimental Approach for the Analysis of the Enantioselective Potential of a New Macrocyclic Receptor for N‐Protected α‐Amino Acids

“…The 1 H NMR spectra of 1 in each of these solvents did not differ significantly, apart from the shifts for the NH signals, and this suggests that the conformation of the macrocycle in solution is not particularly effected by solvent polarity, but the spectrum was better resolved in the more polar solvent (Figure 3). This is in sharp contrast to macrocycle 2, [1] which has a significantly different conformation in CDCl 3 than in [D 6 ]DMSO or CD 3 CN, but is not surprising considering the flexibility of that receptor compared to the rigidity of the monomer analogue.…”

“…Design of macrocycle 1 was based on the highly enantioselective receptor 2 [1] but with a smaller cavity and just one carboxylate binding site. X-ray structural studies and 1 H NMR spectra in CDCl 3 , CD 3 CN or [D 6 ]DMSO show that the macrocycle has a rigid backbone and adopts essentially the same conformation in solvents of different polarity, although the thiourea moiety is able to twist in or out of the cavity.…”

“…[1] Treatment with one equivalent of thiophosgene gave mono-A C H T U N G T R E N N U N G isothiocyanate 4, and subsequent intramolecular reaction between the remaining amino group and the isothiocyanate group gave macrocycle 1 in 17 % yield.…”

“…[ [45] The equilibration of the CH 3 CN solvent box is described in detail elsewhere. [1] Overlapping solvent molecules and those giving rise to repulsive interactions with macrocycle:ligand systems were first deleted. Next, substructures consisting of three shells were created.…”

“…Systems 1 and 2 were prepared by introducing the macrocycle and enantiomer to a previously equilibrated 512 molecule DMSO cubic box (39.28 39.28 39.28 ) at experimental density (1.096 g cm À3 ). [1,45] Overlapping solvent molecules and those giving rise to repulsive interactions were then deleted. Next, three substructures or shells were created, as for the MD simulations in CH 3 CN.…”