邁向海洋分枝桿菌脂多醣 IV 型之寡醣片段結構的合成以及α-(1→4)半乳雙醣的合成

Abstract

胺基醣廣泛存在於天然物分子中，例如脂多醣、醣脂質、核甘酸以及抗生素等。胺基醣參與許多生化作用，例如免疫調節和細胞辨識，因此科學家致力研究和探討含有胺基醣的寡糖合成為重要課題。 四-胺基-四,六雙去氧半乳醣大多存在於細菌的脂多醣，例如Treponema medium脂多醣、M. marinum脂多醣IV型，此四-胺基雙去氧半乳醣常以1,2順式糖苷鍵與其他醣基構成多醣片段，我們以四-疊氮基-四,六-雙去氧半乳醣硫體作為醣予體採用NFM調控醣基化反應和新開發的迭代外源親核性基調控醣基化反應，與不同的醣受體進行反應，而迭代外源親核性基調控醣基化反應，不需要特殊的保護基就可以獲得較佳α選擇性。在M. marinum脂多醣IV型中末端結構為N-醯化四-胺基-四,六-雙去氧半乳醣，與四-胺基-四,六-雙去氧半乳醣相接的pyrrolidone基團分別為Za、Zb、Zc，我們也試著合成類pyrrolidone基團，另外我們以NFM調控醣基化反應的方法應用於含有四-胺基-四,六雙去氧半乳醣之M. marinum脂多醣IV型的片段結構，以及邁向M. marinum脂多醣IV型寡糖片段的合成。

Amino sugars are widely existed in natural products, such as lipopolysaccharides, glycolipids, nucleotides, and antibiotics. It can involved in many biological functions, such as immune modulation, cell recognition; therefore, chemical synthesis of aminosugar-containing oligosaccharides are more important issue. 4-amino-4,6-dideoxy-Galp are mostly existed in lipopolysaccharides of bacteria, such as lipopolysaccharides of Treponema medium、lipopolysaccharides IV of M. marinum. 4-amino-4,6-dideoxy-Galp usually linked with glycosyl residues by 1,2-cis glycosidic linkages to form polysaccharides. We employed a NFM-modulating glycosylation and a novel iterative modulating glycosylation for 4-azido-4,6-dideoxy- thiogalactoglycosides with different glycosyl acceptors to construct 1,2-cis glycosides. The novel iterative modulating glycosylation provide a mild and convenient entry without protecting group manipulation to be able to afford high 1,2 cis-selectivity. M. marinum LOS-IV is terminated with a family of N-acylated 4-amino-4,6-dideoxygalactopyranose residues which contain a pyrrolidone group, Za, Zb and Zc. We also try to synthesize angulous pyrrolidone group which is resembled natural pyrrolidone group, Zb, in M. marinum LOS-IV. We also extended NFM-modulating glycosylation toward synthesis of oligosaacharide fragments of Mycobacterium marinum lipooligosaaccharide IV.