TY - BOOK

T1 - Carbo Diem

T2 - Towards the ideal glycosylation

AU - Nielsen, Michael Martin

PY - 2021

Y1 - 2021

N2 - Stereoselective formation of 2-deoxy-β-glycosides under mild conditions remains a central challenge in the field of carbohydrate chemistry. Current state-of-the-art methods for 2-deoxy-β-glycosylation rely on cryogenic reaction conditions and harsh reaction con-ditions, confining these methods primarily to small-scale synthesis as well as limiting the scope of the synthetic procedures.In the following, the attempted development of a mild 2-deoxy-β-glycosylation using bis-thiourea hydrogen-bond-donor catalysts is described. Initially, a highly β-selective strategy was developed by screening a small library of catalysts, using a benzyl-protected glycosyl chloride as a model electrophile (Scheme 1). Unfortunately, it was found that this glycosylation only allowed a very narrow scope of substrates, prompting a reconsid-eration of the reaction design. It was hypothesized that the shortcomings could be caused simply by the large, steric bulk of the chosen model electrophile, making catalyst-elec-trophile interactions very weak and leaving very little space in the catalytic site for a nucleophile to approach.Installation of smaller allyl protective groups was found as a possible solution to these shortcomings, allowing a wider range of nucleophiles to undergo glycosylation under the reaction conditions. Furthermore, the use of conformationally restricted glycosyl electrophiles was surveyed as a means of increasing the stereoselectivity of the glycosylation reaction. Although only very few experiments were conducted to investigate this, it does indeed seem that conformationally restricted electrophiles lead to higher stereoselectivity, which indicates the future direction of the project described herein.

AB - Stereoselective formation of 2-deoxy-β-glycosides under mild conditions remains a central challenge in the field of carbohydrate chemistry. Current state-of-the-art methods for 2-deoxy-β-glycosylation rely on cryogenic reaction conditions and harsh reaction con-ditions, confining these methods primarily to small-scale synthesis as well as limiting the scope of the synthetic procedures.In the following, the attempted development of a mild 2-deoxy-β-glycosylation using bis-thiourea hydrogen-bond-donor catalysts is described. Initially, a highly β-selective strategy was developed by screening a small library of catalysts, using a benzyl-protected glycosyl chloride as a model electrophile (Scheme 1). Unfortunately, it was found that this glycosylation only allowed a very narrow scope of substrates, prompting a reconsid-eration of the reaction design. It was hypothesized that the shortcomings could be caused simply by the large, steric bulk of the chosen model electrophile, making catalyst-elec-trophile interactions very weak and leaving very little space in the catalytic site for a nucleophile to approach.Installation of smaller allyl protective groups was found as a possible solution to these shortcomings, allowing a wider range of nucleophiles to undergo glycosylation under the reaction conditions. Furthermore, the use of conformationally restricted glycosyl electrophiles was surveyed as a means of increasing the stereoselectivity of the glycosylation reaction. Although only very few experiments were conducted to investigate this, it does indeed seem that conformationally restricted electrophiles lead to higher stereoselectivity, which indicates the future direction of the project described herein.

UR - https://soeg.kb.dk/permalink/45KBDK_KGL/1pioq0f/alma99124088550705763

M3 - Ph.D. thesis

BT - Carbo Diem

PB - Department of Chemistry, Faculty of Science, University of Copenhagen

ER -