Organocatalyzed Cascade Reaction in Carbohydrate Chemistry

Abstract

The extensive and extremely strong development of organocatalysis over the last years provided versatile methodologies for convenient utilization of the carbonyl function of unprotected carbohydrates in C-C-bond formation processes. These biomimetic amine-activated mechanisms enable multiple cascade-protocols for the synthesis of a large scope of carbohydrate derived compound classes. Several, only slightly different protocols have been developed for the application of 1.3-dicarbonyls in stereoselective chain-elongation of unprotected carbohydrates and the synthesis of highly functionalized C-glycosides of defined configuration. Furthermore, the latter class of compounds can also be accessed by the use of methyl ketones. So a high substrate scope is available for the installation of desired functionalities in C-glycosides. By a one-pot, operationally simple cascade reaction of isocyanides with unprotected aldoses and amino acids an access to a broad range of defined glycosylated pseudopeptides is given. The elaborated organocatalyzed cascade-reactions provide defined access to highly functionalized carbohydrate derivatives. Depending on the reaction conditions different origin to control the installation of configuration during the bond-formation process were observed. The demonstrated organocatalyzed cascade sequences indicate the great potential of unprotected carbohydrates in the synthesis of highly functionalized bio-mimetic structure motifs by operationally simple, one-pot protocols.Due to the great biological importance of carbon chain elongated carbohydrates, the synthesis of this structural diverse compound class has attracted high synthetic interest from the scientific community. Among the elongated carbohydrates, C-Glycosides have gained considerable importance over the last few decades, since they are configuratively stable under enzymatic conditions and less prone to cleavage at the anomeric carbon. As such they are appealing substrates for chemical biology and medicinal chemistry.