Journal of Carbohydrate Chemistry最新文献

Glycosphingolipids (GSLs) are a subclass of glycolipids made of a glycan and a ceramide that, in turn, is composed of a sphingoid base moiety and a fatty acyl group. GSLs represent the vast majority of glycolipids in eukaryotes, and as an essential component of the cell membrane, they play an important role in many biological and pathological processes. Therefore, they are useful targets for the development of novel diagnostic and therapeutic methods for human diseases. Since sphingosine was first described by J. L. Thudichum in 1884, several hundred GSL species, not including their diverse lipid forms that can further amplify the number of individual GSLs by many folds, have been isolated from natural sources and structurally characterized. This review tries to provide a comprehensive survey of the major GSL species, especially those with distinct glycan structures and modification patterns, and the ceramides with unique modifications of the lipid chains, that have been discovered to date. In particular, this review is focused on GSLs from eukaryotic species. This review has listed 251 GSL glycans with different linkages, 127 glycans with unique modifications, 46 sphingoids, and 43 fatty acyl groups. It should be helpful for scientists who are interested in GSLs, from isolation and structural analyses to chemical and enzymatic syntheses, as well as their biological studies and applications.

A diacyl phosphatidylinositol (PI) derivative with an azide linked to its inositol C4-position was effectively synthesized in 19 steps for the longest linear sequence and in a ca. 1% overall yield from 1,2-distearoyl-sn-glycerol and D-glucose. This compound was designed as a biosynthetic precursor of glycosylphosphatidylinositol (GPI) anchors. Its azide would enable further modification to introduce other molecular tags by a biocompatible click reaction. Therefore, it can be a useful probe for metabolic engineering of cell surface GPI anchors and GPI-anchored proteins.

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Arabinogalactan (ICPA) was isolated from the medicinal plant Ixeris chinensis (Thunb.) Nakai, and was used as the reducing agent to stabilize selenium nanoparticles (SeNPs). ICPA-decorated SeNPs (ICPA-SeNPs) were synthesized with Na₂SeO₃ and ICPA, and their average diameter was 82.6 ± 2.5 nm. ICPA-SeNPs had good dispersity in phosphate-buffered saline (PBS) with a hydrodynamic size of 156.2 ± 2.8 nm. They were stable in PBS solution with a zeta potential of −24.8 ± 0.6 mV. The anti-hepatoma activity of ICPA-SeNPs was investigated in vitro. ICPA-SeNPs significantly suppressed the growth of SMMC-7721 and HepG2 hepatoma cells. They entered SMMC-7721 cells via energy- and caveolae-dependent endocytosis. ICPA-SeNPs were able to increase reactive oxygen species levels, reduce mitochondrial membrane potential, and increase caspase-3 expression in SMMC-7721 cells, which led to the apoptosis of SMMC-7721 cells. They also arrested the cell cycle of SMMC-7721 cells in the S phase. These findings indicate that ICPA could enhance the stability of SeNPs and inhibit SMMC-7721 cell proliferation via the mitochondrial pathway. ICPA-SeNPs could be developed as an antitumor agent for hepatocellular carcinoma treatment.

6′-Sialolactose-modified mono- and bivalent nanobodies were designed and synthesized by a chemoenzymatic strategy. Epidermal growth factor receptor (EGFR)-targeting 7D12 nanobodies, including mono- and bivalent 7D12, were recombinantly expressed in Escherichia coli. Triglycine-modified 6′-sialolactose derivative was synthesized in nine steps. The conjugation of carbohydrates with nanobodies was achieved by Sortase-A mediated ligation with high conversion rates. The obtained glycoengineered nanobodies were finally verified by SDS-PAGE, western blot, and mass spectrometry.

Based on the capability of silyl ethers for efficient glycosylation, the new MTEAN glycosylation protocol utilizing 8-methyltosylaminoethynyl-1-naphthyl (MTEAN) glycosides as donors were extended to one-pot synthesis of nucleosides, late-stage modification of bioactive molecules, and stereoselective construction of 1,2-cis-glucosidic linkages using silyl ethers of the acceptors. Moreover, the reaction mechanism was systematically investigated by control reactions and side product characterizations, leading to the determination of a TfOH-catalyzed ynamide functionality-initiated process, which was further corroborated by identifications of the departure form of leaving group and the real catalyst.

A new route for the synthesis of tetrahydrocortisone 3-glucuronide has been developed with cortisone acetate as a starting material. The key step was using lithium tri-tert-butoxyaluminum hydride to reduce the C-3 carbonyl group of 5β-dihydrocortisone acetate (8) to provide 3α-5β-tetrahydrocortisone acetate (5). Then, Koenig–Knorr method was used for glycosylation with glycosyl bromide as the donor, cadmium carbonate as promoter and 4Å molecular sieves as dehydrating agent to give high yield of the desired product. The new route is shorter and gives higher yield than that reported in the literature.

Extracts of Salacia, which are woody climbers mainly distributed in South Asian countries, have long been used to treat type-2 diabetes. Eight sulfonium-type α-glucosidase inhibitors salacinol, kotalanol, ponkoranol, salaprinol and their corresponding de-O-sulfonated analogues have been isolated so far. The unique structures, as well as distinguished biological activities, made them attractive targets in diverse research disciplines. The development of facile synthetic approaches is critical and fundamental for other extended investigations, including chemical biology and pharmaceutical development. This report provides an overview of the recent synthetic efforts directed toward the assembly of these sulfonium-containing polyhydroxylated natural products. This review will be helpful to gather insights into the development of a novel sulfonium type molecules with potential therapeutic applications.

A novel, straightforward, and environmentally friendly direct coupling procedure to immobilize carbohydrates on solid supports is presented. A characterization study showed that all amino groups on solid supports participated in the linkage with a carbohydrate unit, implicating that the surface load can be easily adjusted by tuning the amination coverage of the surface. Most importantly, the integrity of the cyclic conformation of the linked sugar unit was demonstrated, a feature that is critical for most of the possible applications of carbohydrate-functionalized surfaces. Furthermore, carbohydrate-immobilized submicron particles synthesized by the direct coupling method, on which lectin profiling experiments were conducted, validated the successfulness of our simplistic approach.

Novel 3H-1,5-benzodiazepine-derived aryl C-glycosides were synthesized in good to excellent yields by the coupling of structurally diverse terminal sugar alkynes, aroyl chlorides and 1, 2-phenylenediamine. The protocol is general, mild and efficient. It was suitable for various terminal sugar alkynes and aroyl chlorides, with 37 selected examples. The sugar substrates include pyranosides, furanosides, and acyclic sugars with sensitive and bulky protecting groups. The aroyl chlorides contain electron-donating, electron-withdrawing and electron-neutral substituents.