Configuration‐Controlled Crystal and/or Gel Formation of Protected d‐Glucosamines Supported by Promiscuous Interaction Surfaces and a Conformationally Heterogeneous Solution State

Abstract

The configuration‐dependent self‐association mode of the two anomers of O‐Ac,N‐Fmoc‐d‐glucosamine, a foldamer building block, leading to gel and/or single crystal formation is described. The β‐anomer of the sugar amino acid (2) forms a gel from various solvents (confirmed by SEM, rheology measurements, NMR, and ECD spectroscopy), whereas the α‐anomer (1) does not form a gel with any solvent tested. Transition from the solution state to a gel is coupled to a concurrent shift of the Fmoc‐groups: from a freely rotating (almost symmetrical) to a specific, asymmetric orientation. Whereas the crystal structure of the α‐anomer is built as an evenly packed 3D system, the β‐anomer forms a looser superstructure of well‐packed 2D layers. Modeling indicates that in the lowest energy, but scarcely sampled conformer of the β‐anomer, the Fmoc‐group bends above the sugar moiety, stabilized by intramolecular CH↔π interactions between the aromatic rings. It is concluded that possessing an extended and promiscuous interaction surface and a conformationally heterogeneous solution state are among the basic requirements of gel formation for a candidate molecule.

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives as pH-Responsive Gelators and Their Applications for Drug Delivery

“…The results are shown in Table 1. Four compounds, including a long-chain alkyl and three aryl derivatives, were selected to prepare the unprotected carbamate derivatives IV (19)(20)(21)(22), as shown in Scheme 2. Their gelation properties are also tested and included in Table 1.…”

“…Sugar-based gelators with stimuli-responsive functional groups can therefore form soft materials with combined applications in ion sensing, chemo sensors, and biomedicine [20,21]. Among the many classes of sugar-based gelators, various D-glucosamine derivatives have been demonstrated as Gels 2023, 9, 445 2 of 21 materials with numerous potential applications from drug delivery to the discovery of new therapeutic agents and methods [22]. Our group has studied various classes of these sugar derivatives, including the functionalization of glucosamine to form amides, ureas, and carbamates.…”

A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex

“…The propyl chains of valproate dock into the S1 pocket, being quite similar in size to Ac-Thr or Ac-Met, the P1 residues preferred by the enzyme. 42 Phe274 is positioned above the glucose ring at a 4.1 A distance (measured at the centroids of the rings) in a near parallel orientation to the plane of the sugar (the angle between the two ring planes is 11.6°) forming a strong CH-p interaction 44,45 with the axial C 1 -H 1 , C 3 -H 3 and C 5 -H 5 moieties of the sugar (Fig. 4D and S9 †).…”