Reagent Controlled Stereoselective Synthesis of α-Glucans

Abstract

The development of a general glycosylation method that allows for the stereoselective construction of glycosidic linkages is a tremendous challenge. Because of the differences in steric and electronic properties of the building blocks used, the outcome of a glycosylation reaction can vary greatly when switching form one glycosyl donor–acceptor pair to another. We here report a strategy to install cis-glucosidic linkages in a fully stereoselective fashion that is under direct control of the reagents used to activate a single type of donor building block. The activating reagents are tuned to the intrinsic reactivity of the acceptor alcohol to match the reactivity of the glycosylating agent with the reactivity of the incoming nucleophile. A protecting group strategy is introduced that is based on the sole use of benzyl-ether type protecting groups to circumvent changes in reactivity as a result of the protecting groups. For the stereoselective construction of the α-glucosyl linkages to a secondary alcohol, a per-benzylated glusosyl imidate donor is activated with a combination of trimethylsilyltriflate and DMF, while activation of the same imidate donor with trimethylsilyl iodide in the presence of triphenylphosphine oxide allows for the stereoselective cis-glucosylation of primary alcohols. The effectiveness of the strategy is illustrated in the modular synthesis of a Mycobacterium tuberculosis nonasaccharide, composed of an α-(1–4)-oligoglucose backbone bearing different α-glucosyl branches.

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

“…As for the preparation of 5 , the Ara f PTFAI 9 , Ara f ABz 10 , and 3,5‐branched pentasaccharide 8 were designed to undergo an orthogonal one‐pot glycosylation reaction. For the synthesis of 8 , the 6‐ O ‐levulinoyl (Lev) glucosyl PTFAI donor 15 and the α‐Ara f ‐(1→3)‐α‐Ara f ‐(1→3)‐Ara f trisaccharide acceptor 14 were planned for the successive assembly of the challenging 1,2‐ cis glucosidic linkages using the TMSI‐Ph 3 PO reagent combination recently developed by Codee and co‐workers . The trisaccharide 14 can be readily prepared by orthogonal one‐pot synthesis starting from the monosaccharide building blocks 17 – 19 .…”

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

“…Fort he synthesis of 8,t he 6-O-levulinoyl (Lev) glucosyl PTFAI donor 15 and the a-Araf-(1!3)-a-Araf-(1!3)-Araf trisaccharide acceptor 14 were planned for the successive assembly of the challenging 1,2-cis glucosidic linkages using the TMSI-Ph 3 PO reagent combination recently developed by Codee and co-workers. [26] Thet risaccharide 14 can be readily prepared by orthogonal one-pot synthesis starting from the monosaccharide building blocks 17-19.…”

A Solution to Chemical Pseudaminylation via Development of a Bimodal Glycosyl Donor to Enable Highly Stereocontrolled α- and β-Glycosylation

“…of DMF, donor 22 gave complete α-selectivity in the glycosylation of acceptor 4. The use of DMF additive was first introduced by Mong et al in 2011 as a strongly axial-selective glycosylation additive [33][34][35][36][37] and recently applied by Codée et al in the synthesis of a complex α-glucan [38] . To the best of our knowledge, this is the first example of the 'DMF effect' in the glycosylation of a ulosonic acid donor.…”