Why Are the Hydroxy Groups of Partially Protected N-Acetylglucosamine Derivatives Such Poor Glycosyl Acceptors, and What Can Be Done about It? A Comparative Study of the Reactivity of N-Acetyl-, N-Phthalimido-, and 2-Azido-2-deoxy-glucosamine Derivatives in Glycosylation. 2-Picolinyl Ethers as Reactivity-Enhancing Replacements for Benzyl Ethers

Abstract

Competition experiments were used to determine that the 4-OH of a 2-deoxy-2-azidoglucose derivative is more reactive than that of the corresponding N-phthalimido glucose derivative which, in turn, is more easily glycosylated than the N-acetyl derivative. Glycosylation of the 4-OH groups of the N,N-diacetyl and N-acetyl-N-benzyl glucosamine was also found to be superior to that of the simple N-acetyl substance. The 3-O-picolinyl ether of a 4,6-O-benzylidene-protected N-acetylglucosamine was shown to have a strong intramolecular hydrogen bond to the adjacent acetamide group. This interaction does not persist in the 3-O-picolinyl-6-O-benzyl N-acetylglucosamine derivative, owing to a probable competing hydrogen bond between the 4-OH and the picolinyl ether. However, in the 3-O-picolinyl-4-O-benzyl N-acetylglucosamine regioisomer the picolinyl-acetamide hydrogen bond persists and leads to an enhancement of reactivity of the 6-OH, over and above that in the corresponding 3-O-benzyl ether, due to disruption of the typical intermolecular amide hydrogen bonding scheme. It is demonstrated that the picolinyl ether is readily removed by hydrogenolysis at atmospheric pressure and room temperature.

A Highly α‐Stereoselective Synthesis of Oligosaccharide Fragments of the Vi Antigen from Salmonella typhi and Their Antigenic Activities

“…[12] Moreover, the Nacetyloxazolidinone functionality also decreases the tendency for amide glycosylation [13] and removes the possibility of problematic hydrogen-bonding networks. [14] Recently, our group has also achieved advances in the stereochemistry of glycosylations by virtue of oxazolidinone protecting-group strategies, [15] and the application of this protecting group to the chemical synthesis of oligosaccharide fragments has been realized. [16] N-Acetyloxazolidinone is not only able to serve as a stereoselective directing group and an orthogonal protecting group, but can also be easily removed by chemoselective deprotection.…”

Synthesis of Pentasaccharide Fragments Related to the O‐Specific Polysaccharide of Shigella flexneri Serotype 1a

“…[81] The N-acetyl-N-benzyl group is also not recommendable for protecting amino groups in glucosamine-containing oligosaccharides, because rotamers at the amide bond complicate assignment of NMR signals considerably. [82][83][84][85] Solely the trifluoroacetyl group appeared to be suitable here because trifluoroacetamides are stable during deprotection of other acyl groups, [89][90][91] but are still easily removed and ensure high β-selectivities and good yields during glycosylation reactions. [86] Thus, the N-trifluoroacetyl-protected glucosamine 4 [86] was first converted into the glucoside 5b in 85 % yield by sequential deprotection with NaOMe in methanol, fol-THF.…”

Stereodirecting Effect of Cyclic Silyl Protecting Groups in Chemical Glycosylation

“…In the glycosidations of 70 with several acceptors including well-known less reactive alcohols, mediated by either the Ph 2 SO/Tf 2 O or NIS/TfOH system, high yields and complete -selectivities are observed. Successful results were obtained by Crich and Dudkin, (2001) even in the glycosylation with the C4 hydroxyl group of glucosamine derivative 71, which is notorious for its poor nucleophilicity (Scheme 4). These results demonstrate the high reactivity of 2,4-DTBS-tethered donor 70 and its general versatility for the synthesis of -glucuronides.…”