Wei Yi, Wang Quanquan, Koh Ming Joo
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544, Republic of Singapore.
Angew Chem Int Ed Engl. 2023 Jan 26;62(5):e202214247. doi: 10.1002/anie.202214247. Epub 2022 Dec 7.
C-Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C-C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox-active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et N) under blue LED illumination to deliver C-alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross-coupling. Through this manifold, innate CO H and NH motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late-stage glycosylation.
C-烷基糖苷和糖蛋白存在于天然产物中，因其在药物设计中作为碳水化合物模拟物的作用而备受重视。然而，一种将糖基供体与易于获得的试剂（源自丰富的羧酸和胺原料）相结合的实用策略尚未构想出来。在此，我们表明，在蓝色发光二极管照射下，镍催化剂在汉茨希酯和碘化锂（或三乙胺）存在下，促进糖基卤化物与脂肪酸或伯胺（一步转化为氧化还原活性亲电试剂）之间的碳-碳偶联，以高非对映选择性提供C-烷基糖苷。机理研究支持光诱导形成烷基自由基，该自由基与原位生成的糖基镍物种反应以促进交叉偶联。通过这种方式，氨基酸和寡肽中嵌入的固有C–OH和N–H基序被选择性封端并官能化，通过后期糖基化得到糖肽缀合物。
