The efficient and stereoselective formation of glycosidic linkages is a common goal in carbohydrate chemistry. Strategies often begin with the activation of a starting species to create an electrophilic oxocarbenium ion intermediate in situ. The oxocarbenium is then trapped by a nucleophile to form a new glycosidic bond. Our group is interested in the synthesis ring expanded carbohydrates, especially seven-membered ring septanoses, and the application of septanosides as surrogates of pyranosides in glycobiology. Here we focus on the details surrounding the synthesis of septanosyl donors from pyranoses and their utilization in glycosylation reactions. Specifically, our recent work on the synthesis and glycosylations of septanosyl fluorides will be highlighted.[1,2] We will also report on our efforts to understand the nature and reactivity of septanosyl oxocarbenium ions.[3] These synthetic and mechanistic efforts set a sound foundation for the synthesis of a variety of septanose glycosides. The preparation of septanosides is a key initial objective that then enables the investigation of their roles in biological contexts, especially as potential carbohydrate based therapeutics.
[1] Septanosyl fluorides as glycosyl donors: Synthesis of 2-amino septanosyl glycoconjugates. J. Saha, M. W. Peczuh, Chem. Eur. J. 2011, 17, 7357-7365.
[2] Glycosylations with a septanosyl fluoride donor lacking a C2 protecting group. J. Saha, M. W. Peczuh Tetrahedron Lett. 2012, 53, 5667-5670.
[3] C2 Hydroxyl Group Governs the Difference in Hydrolysis Rates of Methyl-(alpha)-D-glycero-D-guloseptanoside and Methyl-(beta)-D-glycero-D-guloseptanoside. J. M. Beck, S. M. Miller, M. W. Peczuh, C. M. Hadad, J. Org. Chem. 2012, 77, 4242-4251.
