We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction. We further demonstrate the utility of this method in the late-stage modification of complex drug molecules, including the anticancer agent camptothecin. Experimental studies provide insight into the reaction mechanism.

Herein, we report a method that enables the synthesis of carbohydrate−DNA conjugates by radical addition. Key to the success is the use of readily available, bench-stable, and unprotected glycosyl sulfinates as precursors to glycosyl radicals. The redox neutral reaction proceeds under mild and simple conditions and tolerates a broad substrate scope. A small library of carbohydrate−DNA conjugates was prepared. D NA-encoded library (DEL) has emerged as a powerful tool for hit identification in academia and pharmaceutical industry. 1 A DEL is a collection of compounds, each of which is linked to a unique DNA sequence. The DNA serves as an identifier for the compound, which allows for the highthroughput screening of large numbers of compounds to identify those binding to a particular target. On the basis of such affinity selection, millions to billions of DNA-encoded molecules can be conveniently screened against biological targets all at once, in a single experiment. Compared with traditional screening strategies, the DEL technology shows advantages in terms of cost, speed, and scale. 2 Shown in Scheme 1a are some representative lead compounds found by DEL technology. 3 To construct structurally diverse and pharmaceutically relevant DELs, the development of DNA-compatible reactions is in high demand. 4 However, the required DNA tag, which is not soluble in most organic solvents and is easily degraded or modified, places stringent requirements on the mildness of a potential synthetic method to be used. 5 In addition, since DNA tags are in highly dilute solution, to modify DNA tags requires a reaction to be efficient even at low concentrations. Methods that fulfill the above requirements are rare.Carbohydrates are extremely valuable organic molecules in nature and are involved in various crucial life-sustaining processes, including immune response, fertilization, and cell− cell interactions. 6 They represent a privileged class of compounds in drug discovery, with over one hundred carbohydrate-based small molecules already marketed to treat various diseases. 7 Considering the structural diversity and biological activity of carbohydrates, to incorporate sugar

Herein, we report a method that enables the synthesis of carbohydrate-DNA conjugates by radical addition, in which the gen-eration of glycosyl radicals from readily available and bench-stable unprotected glycosyl sulfinates is the key. These reactions were carried out under mild conditions and tolerate a broad substrate scope.

Herein, we report a method that enables the synthesis of carbohydrate-DNA conjugates by radical addition, in which the gen-eration of glycosyl radicals from readily available and bench-stable unprotected glycosyl sulfinates is the key. These reactions were carried out under mild conditions and tolerate a broad substrate scope.

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction. We further demonstrate the utility of this method in the late-stage modification of complex drug molecules, including the anticancer agent camptothecin. Experimental studies provide insight into the reaction mechanism.