2-Acetamido-2-deoxy-D-glycopyranosides subunits constitute the core structural elements prevalent in a large number of living organisms as oligosaccharides and glycoconjugates, and could serve as metabolic substrates for cell surface engineering. Octahydropyrano[3,2-b]pyrrole, which combines a pyrrole segment to 2-amino- C-glycoside backbone, is a potential glycosidase inhibitor.

Many methods to synthesize the analogous construction have been reported. While it is unfortunate that most of these methods are not the ideal for utilizing expensive reagents, or resulting poor stereoselectivities. Prof. SHAO Huawu’s group of Chengdu Institute of Biology, Chinese Academy of Sciences has long been committed to the study of carbohydrates, especially the iminosugar C-glycosides. Recently, they developed a convenient and highly stereoselective method for synthesis of octahydropyrano[3,2-b]pyrrole derivatives.

The octahydropyrano[3,2-b]pyrrole derivatives are synthesized by a double reductive amination from pyranose derivatives of nono-2,5-diuloses and octos-4-uloses and various amines. Initial studies were performed with NaCNBH3 in MeOH using n-butylamine as aminating reagent at 0℃, but the reaction was so complex that no major product could be detected by TLC. Then, NaBH(OAc)3, which is a powerful and versatile reducing reagent for the reductive amination, was used. In order to find a suitable condition for the experiments, an optimization on the solvent, the amounts of NaBH(OAc)3 and HOAc were executed.

Fortunately, the reaction could proceed smoothly in all solvents including dichloroethane, dichloromethane, acetonitrile and tetrahydrofuran. Dichloromethane was the best solvent, and dichloroethane was also efficient, while the acetonitrile and tetrahydrofuran were not as good as the former solvents. After variation of the amount of reducing agent and acetic acid, it was found that the double reductive amination could be proceeded smoothly with 3.0 equiv of NaBH(OAc)3 and 2.0 equiv of HOAc in CH2Cl2 at room temperature.

This work provides a new approach to the octahydropyrano[3,2-b]pyrrole derivatives, which is applied to the synthesis of castanospermine analogues. The paper entitled "A convenient and highly stereoselective method for synthesis of octahydropyrano[3,2-b]pyrrole derivatives" was published in Carbohydrate Research (2013, 366, 55-62).