Oxidant-Controlled Heck-Type <i>C</i>-Glycosylation of Glycals with Arylboronic Acids: Stereoselective Synthesis of Aryl 2-Deoxy-<i>C</i>-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/O2, 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

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-Ir³⁺(ppy)₃ as the photocatalyst, Umemoto’s 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

Nitro-polyols via Pyridine Promoted CC Cleavage of 2‑Nitroglycals. Application to the Synthesis of (−)-Hyacinthacine A1

A mild and convenient transformation for the synthesis of nitro-polyols is described. The nitro-polyol derivatives were prepared either from 2-nitroglycals via a pyridine-promoted scission of the carbon–carbon double bond or from glycals via a sequential nitration–scission procedure. The generated nitro-polyols could undergo a stereoselective Michael addition reaction. The utility of the addition products was exemplified by the concise synthesis of (−)-hyacinthacine A1 and 7a-<i>epi</i>-(−)-hyacinthacine A1

“Ring Opening–Ring Closure” Strategy for the Synthesis of Aryl‑<i>C</i>‑glycosides

A new “ring-opening–ring closure” strategy for the synthesis of aryl-<i>C</i>-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-<i>C</i>-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph₃PHBr or Sc­(OTf)₃ mediated ring closure reaction provided α- or β-preferred aryl-<i>C</i>-Δ^2,3-glycosides, respectively. Furthermore, β-d-phenyl-<i>C</i>-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-d-phenyl-<i>C</i>-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu₃SnH/AIBN, the synthesis of 2-deoxy-aryl-<i>C</i>-glycosides was ultimately realized in a stereoselective manner

Visible Light Photoredox-Catalyzed <i>O</i>‑Sialylation Using Thiosialoside Donors

An efficient protocol for the O-sialylation using thiosialoside donors under visible light photocatalysis was developed. Thiosialosides were activated under the irradiation with blue light in the presence of Ru­(bpy)₃(PF₆)₂ as photocatalyst, Umemoto’s reagent as CF₃ radical source and Cu­(OTf)₂ as an additive in acetonitrile/dichloromethane at −30 °C, and the subsequent reaction with glycosyl acceptors generally produced the desired sialosides in good to excellent yields with the satisfactory α-selectivity

<i>O</i>‑Glycosylation Enabled by <i>N-</i>(Glycosyloxy)acetamides

A novel glycosylation protocol has been established by using <i>N</i>-(glycosyloxy)­acetamides as glycosyl donors. The <i>N</i>-oxyacetamide leaving group in donors could be rapidly activated in the presence of Cu­(OTf)₂ or SnCl₄ under microwave irradiation. This glycosylation process afforded the coupled products in high yields, and the reaction enjoyed a broad substrate scope, even for disarmed donors and hindered acceptors. The easy availability of the donors, the high stability of <i>N-</i>(glycosyloxy)­acetamides, and the small leaving group make this method very practical

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-<i>N</i>-glycolylsialyl-(2,4)-α-<i>N</i>-acetylsialyl-(2,6)-glucoside, was assembled by stereoselective coupling of a 5-<i>N</i>,4-<i>O</i>-carbonyl-protected sialyl phosphate donor, a <i>N</i>-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

DataSheet1_Electrochemical Bromination of Glycals.docx

Herein, the convenient one-step electrochemical bromination of glycals using Bu4NBr as the brominating source under metal-catalyst-free and oxidant-free reaction conditions was described. A series of 2-bromoglycals bearing different electron-withdrawing or electron-donating protective groups were successfully synthesized in moderate to excellent yields. The coupling of tri-O-benzyl-2-bromogalactal with phenylacetylene, potassium phenyltrifluoroborate, or a 6-OH acceptor was achieved to afford 2C-branched carbohydrates and disaccharides via Sonogashira coupling, Suzuki coupling, and Ferrier rearrangement reactions with high efficiency. The radical trapping and cyclic voltammetry experiments indicated that bromine radicals may be involved in the reaction process.</p

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 <b>48</b><i><b>l</b></i> with a <i>K</i>_i 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

Electrochemical Trifluoromethylation of Glycals

Carbohydrates play essential roles in various physiological and pathological processes. Trifluoromethylated compounds have wide applications in the field of medicinal chemistry. Herein, we report a practical and efficient trifluoromethylation of glycals by an electrochemical approach using CF3SO2Na as the trifluoromethyl source and MnBr2 as the redox mediator. A variety of trifluoromethylated glycals bearing different protective groups are obtained in 60–90% yields with high regioselectivity. The successful capture of a CF3 radical indicates that a radical mechanism is involved in this reaction