Synthesis of Rare 6-Deoxy-D-/L-Heptopyranosyl Fluorides: Assembly of a Hexasaccharide Corresponding to Campylobacter jejuni Strain CG8486 Capsular Polysaccharide
Synthesis of Rare 6-Deoxy-D-/L-Heptopyranosyl Fluorides: Assembly of a Hexasaccharide Corresponding to Campylobacter jejuni Strain CG8486 Capsular Polysaccharide
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DOI：
10.1021/jacs.1c05048
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发表时间：
2021-07-14
影响因子：
15
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Li, Tiantian;Wang, Jianjun;Li, Ming
空肠弯曲菌（Campylobacter jejuni）是引起人类消化道疾病的主要病原菌，已被世界卫生组织列为高度耐药病原菌之一。梭空肠荚膜多糖的特征在于广泛存在不常见的6dHepp残基，并且已被证明是开发创新的抗菌糖缀合疫苗的潜在抗原。为了解决罕见的6dHepp结构的重要性的合成方法的缺乏，我们在此描述了一种新的和有效的方法，用于制备不常见的n-/L-6dHepp氟化物，具有作为糖基化剂的权力。该合成是通过C1-至-C5的转换策略实现的，该策略依赖于由容易获得的烯丙基D-C-糖苷产生的糖醛酸的自由基脱羧还原。为了进一步展示该方案的应用，结构独特的六糖由-> 3）-β-D-6 didoHepp-（1 -> 4）-β-D-GlcpNAc-（1 -> 4）单元组成，对应于C.空肠菌株CG 8486首次被组装。该组装体的特征在于通过β-（1，2-反式）-D-古罗-庚吡喃糖苷的C2构型的反转来高效构建具有合成挑战性的β-（1，2-顺式）-D-吲哚-庚吡喃糖苷，所述β-（1，2-反式）-D-古罗-庚吡喃糖苷通过正交保护的6dgulHepp氟化物的手性辅助立体选择性糖基化方便地获得。6dHepp氟化物和由此产生的聚糖的容易获得性可以作为进一步开发对抗弯曲杆菌感染的合成疫苗的合理起点。
Campylobacter jejuni is the leading cause of human diarrheal diseases and has been designated as one of highly resistant pathogens by the World Health Organization. The C. jejuni capsular polysaccharides feature broad existence of uncommon 6dHepp residues and have proven to be potential antigens to develop innovative antibacterial glycoconjugation vaccines. To address the lack of synthetic methods for rare 6dHepp architectures of importance, we herein describe a novel and efficient approach for the preparation of uncommon n-/L-6dHepp fluorides that have power as glycosylating agents. The synthesis is achieved by a C1-to-C5 switch strategy relying on radical decarboxylative fluorination of uronic acids arising from readily available allyl D-C-glycosides. To further showcase the application of this protocol, a structurally unique hexasaccharide composed of -> 3)-beta-D-6didoHepp-(1 -> 4)-beta-D-GlcpNAc-(1 -> units, corresponding to the capsular polysaccharide of C. jejuni strain CG8486 has been assembled for the first time. The assembly is characterized by highly efficient construction of the synthetically challenging beta-(1,2-cis)-D-ido-heptopyranoside by inversion of the C2 configuration of beta-(1,2-trans)-D-gulo-heptopyranoside, which is conveniently obtained by anchimerically assisted stereoselective glycosylation of the orthogonally protected 6dgulHepp fluoride. Ready accessibility of 6dHepp fluorides and the resulting glycans could serve as a rational starting point for the further development of synthetic vaccines fighting Campylobacter infection.