Improved hemicryptophane hosts for the stereoselective recognition of glucopyranosides

Abstract

Four new enantiomerically and diastereomerically pure hemicryptophane hosts (M-SSS-2/P-SSS-2 and M-RRR-2/P-RRR-2 pairs) were designed for the recognition of sugar derivatives. Their absolute configuration was determined from the circular dichroism spectra and DFT calculations. The host molecules were then used for the stereoselective recognition of glucopyranosides. Binding constants were obtained from (1)H NMR titration experiments showing an increase of affinity for this class of receptors, associated with an improved diastereo- and enantio-differentiation.

Large‐Scale Synthesis of Enantiopure Molecular Cages: Chiroptical and Recognition Properties

“…Nevertheless, the applications of such enantiopure cages are highly limited because of difficulties in accessing them. For instance, until now, enantiopure hemicryptophanes have been obtained in two different ways: 1) either through chiral resolution of the racemic mixture by HPLC, or 2) through the introduction of stereogenic centers to form diastereomers (compounds PSSS ‐ 1 and MSSS ‐ 1 ; Figure ) . The first strategy affords only a few milligrams of enantiopure product or is unsuccessful in many cases, whereas the second one provides enantiomerically pure compounds, but the related synthetic pathway involves many more steps than the synthesis of the racemic mixture, followed by a tedious separation of the diastereomers formed with very low overall yields.…”

Cyclotriveratrylene-BINOL-Based Host Compounds: Synthesis, Absolute Configuration Assignment, and Recognition Properties

“…[25][26][27][28][29][30] The related hemicryptophanes combine a CTV moiety with another C 3 symmetrical unit and display chiral recognition properties towards molecules of biological interest like neurotransmitters and carbohydrates. [31][32][33][34][35][36] Although the efficiency and selectivity of these two classes of cage compounds were demonstrated, their quite complex and low yield syntheses raise the question about the potential applications of such sophisticated structures. [34][35][36][37][38][39] Thus, we decided to investigate the chiral recognition properties of "openshell" enantiopure CTV units: their synthesis avoids the macrocyclization step, and therefore should be easier and shorter.…”

“…[31][32][33][34][35][36] Although the efficiency and selectivity of these two classes of cage compounds were demonstrated, their quite complex and low yield syntheses raise the question about the potential applications of such sophisticated structures. [34][35][36][37][38][39] Thus, we decided to investigate the chiral recognition properties of "openshell" enantiopure CTV units: their synthesis avoids the macrocyclization step, and therefore should be easier and shorter. However, such hosts are expected to be more flexible and less pre-organized than their cage counterparts and thus supposed to be less efficient and selective.…”

Closed vs Open‐Shell CTV Based Host Compounds: A Direct Comparison

“…Cryptophanes combine two CTV moieties and have shown remarkable enantioselective recognition properties of small chiral molecules like epoxides or the simple halogenoalkane CHFClBr . The related hemicryptophanes, which are built from the association of a CTV with another C 3 symmetrical unit, are heteroditopic hosts able to recognize chiral molecules of biological interest such as neurotransmitters and carbohydrates . Recently, we reported the synthesis and the enantioselective recognition properties of the “open‐shell” enantiopure CTV stereoisomers 1 (Figure ), which combine both the axial chirality of the binaphthol units with the inherent chirality of the CTV .…”