2023 Fiscal Year Final Research Report
Flow synthesis and characterization of onjisaponins for the creation of vaccine adjuvants
Project/Area Number |
21K14796
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 38040:Bioorganic chemistry-related
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Research Institution | Kitasato University |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | オンジサポニン / フロー合成 / オレアノール酸 / 配糖化 |
Outline of Final Research Achievements |
In order to establish the total synthetic route of onjisaponins, the following basic reaction conditions were investigated by using oleanolic acid substarate, which is similar to the aglycon skeleton of onjisaponins. (1) Application of microfluidic C-3 glycosylation; (2) Regioselective cinnamoylation of D-fucose and intramolecular rearrangement reaction. The use of microflow reactors was effective in the glycosylation of low-reactive deoxysugars such as D-fucose. Regioselective cinnamoylated compounds could be synthesized with the use of the borinic acid-type catalyst (2-aminoethyl diphenylborinic acid), and the nucleophilic base, (quinuclidine) by using saponin, which became available in large quantities, as a substrate.
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Free Research Field |
有機合成化学
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Academic Significance and Societal Importance of the Research Achievements |
オンジサポニン類のように糖鎖構造にシンナモイル基が結合する配糖体の合成は、縮合反応や脱保護段階でカラム分離不可能なcis/trans異性体を生じやすい課題があった。本研究の成果である合成終盤段階でのサポニン糖鎖直接的Cin基導入法は、異性体を生じる課題の解決策として天然配糖体や誘導体合成への利用を期待できる。また、開発が求められている次世代型の粘膜ワクチンは皮下接種ワクチンと比較して病原体の初発感染を防ぐ抗原特異的分泌型IgAの産生や変異抗原にも対応できる交叉免疫の付与が可能である。今後本課題を達成することで、臨床応用例の少ない経鼻接種インフルエンザ粘膜ワクチンアジュバントの実用化に繋がる。
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