C-Silylated Glycosyl Donors

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Martin J Pedersen1, Christian Marcus Pedersen2

1University College Dublin, Dublin, Ireland, 2University of Copenhagen, Copenhagen, Denmark

In glycosylation chemistry the influence of protective groups has received a considerable amount of interest in recent decades. It was recognized by Paulsen that acetyl ester groups deactivated the glycosyl donors compared to benzyl ethers.[1] This was later used by Fraser-Reid to develop the concept of armed-disarmed glycosyl donors.[2] Bulky silyl ethers on trans-vicinal hydroxyl groups have been found to induce a conformational change on the pyranoside ring, which greatly increases the anomeric reactivity.[3] Such donors are referred to as conformational super-armed donors. However, all functional groups found on sugars in the biosphere are inherently electron-withdrawing, in comparison to carbon. With the exception of deoxy-glycosides that are considered the upper limit of reactivity for glycosyl donors. 2-Deoxy glycosyl donors, with a methylene group adjacent to the anomeric center, often lead to uncontrollable and unselective reactions, as deoxy positions do not bear any conformational influence. Therefore, it is interesting to study how electron-donating groups with steric bulk can influence the reactivity of a glycosyl donor. 

Relatively few functional groups are electron-donating relative to carbon, and even fewer would be compatible with glycosylation conditions. To fulfil these requirements only silicon stands out, since it is comparably less electron-withdrawing than both H and C, and forms stable bonds with both elements. The introduction of Si directly onto the sugar scaffold would allow for investigation of two interesting effects. The stereo electronics, as it would be reversed compared to oxygen-bearing analogues, and the bulk of having a tetravalent atom directly bound to the pyranoside-scaffold. Despite these interesting perspectives no such compounds have been synthesized nor investigated and no well-proven methods for the installation of such groups onto highly functionalized polyols are existent to our knowledge. 

In this study we investigated how to introduce a C-Si bond on to the 4-position of a glycopyranosyl donor, resembling 3 deoxy glucosyl and mannosyl derivatives. We showed how these donors could be synthesized on gram scale and investigated their glycosylation properties in detail (see Figure 1). 

Figure 1. We developed a synthesis route to 4-C-silylated glycosyl donors, starting from cellulose and investigated their glycoslylation properties in detail. 

  1. Paulsen, H. Angew. Chemie Int. Ed. English 1982, 21 (3), 155–173.
  2. Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J. Am. Chem. Soc. 1988, 110 (16), 5583–5584.
  3. Pedersen, C. M.; Nordstrøm, L. U.; Bols, M. J. Am. Chem. Soc. 2007, 129 (29), 9222–9235.