De-Cai Xiong

Oxidant-Controlled Heck-Type C-Glycosylation of Glycals with Arylboronic Acids: Stereoselective Synthesis of Aryl 2-Deoxy-C-glycosides

Oxidative Heck-type C-glycosylations of glycals with various arylboronic acids using Pd(OAc)(2) as catalyst in the presence of oxidant were developed. The corresponding ketone, enol ether, and enone types of C-glycosides were predictably obtained with benzoquinone (BQ), Cu(OAc)(2)/O(2), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as oxidants, respectively. This method provides a simple, mild, and stereoselective synthesis of aryl 2-deoxy-C-glycosides.

Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

Stereoselective Koenigs–Knorr Glycosylation Catalyzed by Urea

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

Direct C–H Trifluoromethylation of Glycals by Photoredox Catalysis

A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemotos reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly. This visible light-mediated trifluoromethylation reaction was highlighted by the trifluoromethylation of the biologically important Neu2en moiety.

Photoinduced C–S Bond Cleavage of Thioglycosides and Glycosylation

A glycosyl coupling reaction via photoinduced direct activation of thioglycosides and subsequent O-glycosylation in the absence of photosensitizer was developed for the first time. This reaction underwent a selectively homolytic cleavage of a C-S bond to generate a glycosyl radical, which was oxidized to an oxacarbenium ion by Cu(OTf)2, and a sequential O-glycosylation. A wide range of glycosides were synthesized in moderate to excellent yield using sugars, amino acids, or cholesterol as the acceptors.

ortho-Methylphenylthioglycosides as glycosyl building blocks for preactivation-based oligosaccharide synthesis

Thioglycosides are widely used in orthogonal glycosylation, armed-disarmed chemoselective glycosylation, and preactivation-based glycosylation. Nevertheless, aglycon transfer occasionally occurred in the glycosylation process of thioglycosides. This problem was also encountered in preactivation-based reactions, which limited the applications of preactivation-based glycosylation to some extent. To tackle this problem, sterically hindered aglycon ortho-methylphenylthioglycosides were introduced as glycosyl building blocks. These thioglycosides prevented the aglycon transfer and enhanced the efficiency of glycosyl coupling reactions, especially in the reactions of disarmed donors with armed acceptors. Moreover, these thioglycosides were employed in preactivation-based one-pot oligosaccharide assembly.

Highly Substituted Cyclopentane–CMP Conjugates as Potent Sialyltransferase Inhibitors

Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs. On the basis of the transition state of the enzyme-catalyzed sialylation reaction, we proposed that the cyclopentane skeleton in its two puckered conformations might mimic the planar structure of the donor (CMP-Neu5Ac) in the transition state. A series of cyclopentane-containing compounds were designed and synthesized by coupling different cyclopentane α-hydroxyphosphonates with cytidine phosphoramidite. Their inhibitory activities against recombinant human ST6Gal-I were assayed, and a potent inhibitor 48l with a Ki of 0.028 ± 0.006 μM was identified. The results show that the cyclopentanoid-type compounds could become a new type of sialyltransferase inhibitors as biological probes or drug leads.

Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents

Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia.

Stereoselective Synthesis of the Trisaccharide Moiety of Ganglioside HLG-2

The glycan portion of ganglioside HLG-2, which was identified in the extracts of the sea cucumber Holothuria leucospilota , was synthesized in a highly efficient and stereoselective manner. The unusual sequence of the trisaccharide moiety, α-N-glycolylsialyl-(2,4)-α-N-acetylsialyl-(2,6)-glucoside, was assembled by stereoselective coupling of a 5-N,4-O-carbonyl-protected sialyl phosphate donor, a N-2,2,2-trichloroethoxycarbonyl (Troc)-protected sialyl acceptor, and a (trimethylsilyl)ethyl-β-glucosyl acceptor in high yield. The synthesis featured the high-yielding construction of two α-sialyl linkages.

Light-driven highly efficient glycosylation reactions

Glycosylation is unarguably the most important reaction in the field of glycochemistry. Photo-initiated reactions hold extraordinary potential in organic synthesis. Herein we report a novel light-driven strategy for the activation of thioglycosides via the merger of a CF3 radical pathway followed by the subsequent glycosylation with glycosyl acceptors. This protocol could efficiently activate thioglycosides, thereby greatly enhancing the substrate scope of reactions. In particular, the glycosylation reactions, which are completely inert under the existing photo-induced glycosylation conditions, proceeded smoothly in high yields. Many common protective groups were well tolerated under the coupling conditions. Both UV and visible light or even sunlight were used as the source of light for the reactions. The high efficiency of this light-driven glycosylation protocol was further highlighted by the rapid one-pot sequential assembly of oligosaccharides.