以一鍋磷酸化-醣基化反應合成鼠疫耶氏桿菌中的內核寡醣

Abstract

存在於革蘭氏陰性菌表面的酯多醣充滿了豐富的碳水化合物抗原，因此對新疫苗及診斷工具上的發展及極重要。在酯多醣的內核寡醣中，D/L-glycero-D-manno-heptoses (Hep)及3-deoxy-D-manno-oct-2- ulosonic acid acid (Kdo)等高碳醣是常見的分子，由於這些高碳醣分子在哺乳動物體內是沒有的，所以內核寡醣對合成化學家而言是一個具有吸引力的研究目標。 我們的研究著重在開發有效率的合成方法來製備含有Hep的寡醣，主要的困難在於沒有市售的七碳醣底物及缺少有效的方法來組裝七碳醣單元。我們以不對稱的α-aminoxylation方法來建構許多七碳醣硫苷單元，發展了一個一鍋化組裝方法，並完成了鼠疫耶氏桿菌中內核四醣的合成。

Lipopolysaccharides (LPSs) exposed to the surface of Gram-negative bacteria constitute a rich pool of carbohydrate antigens for development of new vaccines and diagnostic tools. Higher carbon sugars such as D/L-glycero-D-manno-heptoses (Hep) and 3-deoxy-D-manno- oct-2-ulosonic acid acid (Kdo) are conserved carbohydrate units in the inner core oligosaccharides of LPSs but absent in mammals. Therefore, such core oligosaccharides (particularly from pathogens) are attractive synthetic targets for organic chemists. Our study focuses on development of efficient synthetic strategies for construction of oligosaccharides containing D/L-glycero-D- mannoheptosyl units. The challenges are no commercially available heptose substrates and lack of efficient method for assemblage of heptosyl building blocks. In our work, new synthetic routes were explored to access D-glycero- and L-glycero-D-manno-heptosyl substrates based on asymmetric α-aminoxylation method. Building on these substrates, various thioglycosides were prepared, which enabled the investigation of a new one-pot assemblage strategy for coupling these precious building blocks. We also demonstrated the utility of this one-pot assemblage in the synthesis of the inner core tetrasaccharide found from the pathogen, Yersinia pestis, a causative agent of Bubonic Plague.