二、三分枝甘露糖簇衍生物的合成

采取一种有效途径合成了二、三分支的甘露糖簇分子．甘露糖经烯丙苷化、乙 酰基保护后，将其烯丙基的双键氧化得到带有羧基连接臂的甘露糖衍生物，然后再 分别与l，6-己二胺和三(2-氨乙基)胺进行缩合反应，最后脱掉保护基，得到二分 枝甘露糖簇化合物6和三分枝甘露糖簇化合物8．     

Chemistry and Biology of Oligovalent β‐(1→2)‐Linked Oligomannosides: New Insights into Carbohydrate‐Based Adjuvants in Immunotherapy

A series of oligovalent carbohydrate assemblies (ranging from mono‐ to pentavalent), derived from three structurally different β‐linked or β‐(1→2)‐linked mannosides, has been chemically synthesized, and the respective compounds have been biologically evaluated in order to investigate their immunostimulatory properties. The Crich methodology for β‐mannosylation was successfully utilized to introduce the β‐linkages, and a click chemistry protocol was utilized to generate the oligovalent derivatives. A convenient protecting group strategy involving the simultaneous use of both p‐methoxybenzyl and benzylidene groups was employed, which allowed a simple and cost‐effective global deprotection step. The immunomodulatory properties of the synthesized multivalent mannosides were evaluated by assessing cytokine production in human white blood cell cultures. The Th2‐type cytokines interleukin‐4 and interleukin‐5 (IL‐4 and IL‐5), the Th1 cytokine interferon‐γ (IFN‐γ), the Treg cytokine IL‐10, and the pro‐inflammatory cytokine tumor necrosis factor (TNF) were included in the screening. A single trivalent acetylated mannobiose derivative was identified as a potent inducer of Treg and Th1 immune response, resulting in strong IL‐10 and moderate IFN‐γ productions dose‐dependently, while inducing no Th2 cytokine response. The immunomodulatory properties of this trivalent mannoside were further studied in vitro in allergen (Bet v)‐stimulated human peripheral blood mononuclear cell cultures of birch pollen allergic subjects. Stimulation with birch pollen induced strong IL‐4 and IL‐5 responses, which could be suppressed by the trivalent acetylated mannobiose derivative. The IL‐10 response was also suppressed, whereas the production of IFN‐γ was strongly enhanced. The results suggest that the identified lead compound has suppressive effects on the Th2‐type allergic inflammatory response and shows potential as a possible lead adjuvant for the specific immunotherapy of allergies.     

Lectin-Triggered Aggregation of Glyco-Gold Nanoprobes for Activity-based Sensing of Hydrogen Peroxide by the Naked Eye

The purpose of this study was to develop a colorimetric assay for detecting hydrogen peroxide (H₂O₂) through a combination of using an aryl boronate (AB) derivative and gold nanoparticles (AuNPs). The unique optical property of AuNPs is applied to design a detection probe. The aggregation of AuNPs could be directly observed as a color change by the naked eye. A mannoside-boronate-sulfide ( MBS ) ligand was designed that contains an arylboronate (AB), a mannoside, and a thiol group. The thiol group bonds covalently with the surface of AuNPs to obtain MBS@AuNPs. The mannoside moiety recognizes concanavalin A (Con A), a lectin with four carbohydrate recognition sites that can specifically recognize the non-reducing end of an α-D-mannoside or α-D-glucoside structure. The AB structure on MBS first reacts with H₂O₂ and then inserts an oxygen atom in the B−H bond, which triggers intramolecular electron rearrangement to cleave the covalent bond, resulting in a MBSt mixture. The MBS or MBSt is then modified to citrate-coated AuNPs (c-AuNPs) to have MBS@AuNPs or MBSt@AuNPs. When the MBS@AuNPs are incubated with Con A, the Con A recognizes multiple mannosides on the surface of the MBS@AuNPs. Subsequently, the MBS@AuNPs aggregate and the solution's color changes from red to purple, but this color change does not occur in the case of MBSt@AuNPs. The phenomenon can be observed by the naked eye.     

Synthesis of an antimetastatic tetrasaccharide β-D-Gal-(1→4)-β-d-GlcpNAc-(1→6)-α-D-Manp-(1→6)-β-D-Manp-OMe

An antimetastatic tetrasaccharide T₁,β-D-Gal-（1→4）-β-D-GlcpNAc-（1→6）-α-D-Manp-（1→6）-β-D-Manp-OMe,was synthesized with two approaches.The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24%overall yield.The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36%overall yield.