In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. NMR-NOESY studies supported by MM3 calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments.

The proline-catalysed asymmetric aldol reaction is usually carried out in highly dipolar aprotic solvents (dimethylsulfoxide, dimethylformamide, acetonitrile) where proline presents an acceptable solubility. Protic solvents are generally characterized by poor stereocontrol (e.g., methanol) or poor reactivity (e.g., water). Here, we report that water/methanol mixtures are exceptionally simple and effective reaction media for the intermolecular organocatalytic aldol reaction using the simple proline as the catalyst.

thio-Glycosides with a pseudo-disaccharide structure are synthesized via aziridine opening reactions starting from glycosyl thioacetates with a one-pot protocol, which affords glycomimetics equipped for easy and stable conjugation to aglycones.

M r = 326.27, monoclinic, P2Jn, a = 9.633(5),, c=11.920(5)A, t= 101.0 (4) ° , V--1442 (2)]~3, Z=4, Dx= 1.50, Din(flotation) = 1.485 Mg m -a, 2(Mo Kt~) = 0.71069 A, /t(Mo Ka) = 0.13 mm -~, F(000) = 680, room temperature, R = 0.045 and R w = 0.065 for 2849 independent reflections with I> 2.5a(/). Since the malonic site is deprotonated and the amidinic site is protonated, the dioxopyrimidine residue assumes a structure with a significant contribution of a mesomeric zwitterionic form in accordance with the charge distribution on the malonic and amidinic sites deducible from the net residual charges computed for the atoms of this ring. Also, an intermolecular interaction between a carbonylic O of the theophylline with the CH group of pyrimidine is in agreement with the positive net charges obtained for this group. Both couples of CO and NH groups of the dioxopyrimidine moiety are engaged in hydrogen bonding with the water molecules in the crystal.