偽胺基酸 (pseudaminic acid， Pse) 屬於九碳酮醣酸 (nonulosonic acids) 家族，廣泛存在於多種革蘭氏陰性病原菌表面醣鏈中，並參與鞭毛形成、細菌運動能力及宿主感染等重要生理功能。由於天然來源中的Pse含量低且分離困難，至今Pse的取得仍高度依賴化學合成且具高度挑戰性。因此，本研究以建立高效率且可衍生化之Pse合成路徑為目標。 本研究以市售之L-古洛糖酸-1，4-內酯作為起始原料，參考相關文獻與實驗室先前研究成果，其中透過選擇性保護及官能基轉換，再利用親核取代反應成功於六碳前驅物骨架的C-2與C-4位置導入疊氮官能基並建構正確的立體組態。研究中藉由一維核磁共振氫譜耦合常數分析、NOESY光譜及X-ray單晶繞射等方式確認關鍵六碳前驅物之立體結構。此外，針對後續氧化與去保護條件進行系統性反應優化，以改善反應效率並避免副反應發生。 在最終合成中，透過氧化及銦粉促進之Barbier反應成功將六碳前驅物延伸為九碳骨架前驅物，再經由臭氧促進雙鍵氧化斷裂與酯基水解最終成功獲得目標分子Pse。所得產物之碳譜數據與文獻結果高度一致，證實本研究所建立之合成路徑具有可行性與正確性。本研究最終以總步驟十六步完成Pse之合成，相較既有方法具備良好操作性，且保留後續於C-5位置的官能基衍生化之潛力，可作為未來發展偽唾液酸衍生物及探討細菌醣生物學的重要基礎。;Pseudaminic acid (Pse) is a nine-carbon sugar commonly found on the surface glycans of Gram-negative pathogenic bacteria. It plays a crucial role in bacterial motility， flagellar assembly， and host–pathogen interactions. Due to its low natural abundance and structural complexity， the efficient chemical synthesis of Pse remains a significant challenge. In this study， a practical synthetic route to pseudaminic acid was developed， starting from commercially available L-gulono-1，4-lactone. Through a sequence of selective protection， functional group transformations， and stereochemical control， key intermediates were successfully prepared. Stereochemical inversion at the C-2 and C-4 positions was achieved via nucleophilic substitution and confirmed by NMR analysis， NOESY experiments， and X-ray crystallography. Additionally， the subsequent reaction conditions were optimized to enhance reaction efficiency and minimize undesired side reactions. Finally， through oxidation and an indium-mediated Barbier reaction， the carbon framework was extended to construct the characteristic nine-carbon skeleton of pseudaminic acid. Subsequent ozonolysis and hydrolysis successfully afforded the target compound. The structure was confirmed by comparing NMR data with literature values. Overall， pseudaminic acid was synthesized in sixteen steps， providing an efficient and versatile platform for the synthesis of Pse derivatives and future studies in bacterial glycobiology.
