School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiang Su 210023, China.
Carbohydrate-Based Drug Research Center, Shanghai Institute of Materia Media, Chinese Academy of Sciences, Shanghai 201203, China.
J Am Chem Soc. 2022 Jun 8;144(22):9980-9989. doi: 10.1021/jacs.2c03138. Epub 2022 May 18.
Sugar nucleotides are essential glycosylation donors in the carbohydrate metabolism. Naturally, most sugar nucleotides are derived from a limited number of common sugar nucleotides by biosynthetic pathways, undergoing single or multiple reactions such as dehydration, epimerization, isomerization, oxidation, reduction, amination, and acetylation reactions. However, it is widely believed that such complex bioconversions are not practical for synthetic use due to the high preparation cost and great difficulties in product isolation. Therefore, most of the discovered sugar nucleotides are not readily available. Here, based on biosynthesis mainly, 13 difficult-to-access sugar nucleotides were successfully prepared from two common sugars D-Man and sucrose in high yields, at a multigram scale, and without the need for tedious purification manipulations. This work demonstrated that biosynthesis, although undergoing complex reactions, is also practical and cost-effective for synthetic use by employing a cascade conversion strategy.
糖核苷酸是碳水化合物代谢中必不可少的糖基化供体。在自然界中，大多数糖核苷酸都是通过生物合成途径从有限数量的常见糖核苷酸衍生而来的，经历了单一或多种反应，如脱水、差向异构化、异构化、氧化、还原、氨化和乙酰化反应。然而，由于制备成本高和产品分离困难，人们普遍认为这种复杂的生物转化不适合用于合成。因此，大多数已发现的糖核苷酸不易获得。在这里，基于生物合成，我们成功地从两种常见的糖 D-Man 和蔗糖中以高产率、大规模、无需繁琐的纯化操作制备了 13 种难以获得的糖核苷酸。这项工作表明，尽管生物合成经历了复杂的反应，但通过级联转化策略，它也具有实际应用价值和成本效益，可用于合成。
