Walke Gulab, Kasdekar Niteshlal, Sutar Yogesh, Hotha Srinivas
Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, MH, India.
Commun Chem. 2021 Feb 15;4(1):15. doi: 10.1038/s42004-021-00452-y.
Clinically approved anti-coagulant Fondaparinux is safe since it has zero contamination problems often associated with animal based heparins. Fondaparinux is a synthetic pentasaccharide based on the antithrombin-binding domain of Heparin sulfate and contains glucosamine, glucuronic acid and iduronic acid in its sequence. Here, we show the formal synthesis of Fondaparinux pentasaccharide by performing all glycosidations in a catalytic fashion for the first time to the best of our knowledge. Designer monosaccharides were synthesized avoiding harsh reaction conditions or reagents. Further, those were subjected to reciprocal donor-acceptor selectivity studies to guide [Au]/[Ag]-catalytic glycosidations for assembling the pentasaccharide in a highly convergent [3 + 2] or [3 + 1 + 1] manner. Catalytic and mild activation during glycosidations that produce desired glycosides exclusively, scalable route to the synthesis of unnatural and expensive iduronic acid, minimal number of steps and facile purifications, shared use of functionalized building blocks and excellent process efficiency are the salient features.
临床批准的抗凝血剂磺达肝癸钠是安全的，因为它不存在通常与基于动物的肝素相关的污染问题。磺达肝癸钠是一种基于硫酸乙酰肝素抗凝血酶结合域的合成五糖，其序列中含有氨基葡萄糖、葡萄糖醛酸和艾杜糖醛酸。在此，据我们所知，我们首次以催化方式进行所有糖苷化反应，展示了磺达肝癸钠五糖的形式合成。合成了设计的单糖，避免了苛刻的反应条件或试剂。此外，对这些单糖进行了相互供体-受体选择性研究，以指导[金]/[银]催化的糖苷化反应，以高度汇聚的[3 + 2]或[3 + 1 + 1]方式组装五糖。糖苷化过程中的催化和温和活化仅产生所需的糖苷、合成非天然且昂贵的艾杜糖醛酸的可扩展路线、最少的步骤和简便的纯化、功能化构建块的共享使用以及出色的工艺效率是其显著特点。
