Novel 1-adamantanylthio sialosides were synthesized and coupled to acceptors under NIS/TfOH promotion conditions. These donors showed higher reactivity than the phenylthio sialosides and could be activated by NIS/TfOH in nitrile solvents at −78 °C to afford improved α-sialylations. With the N-acetyl-5-N,4-O-oxazolidinone protected 1-adamantanylthio sialyl donor, high α-selectivities could be achieved in the sialylations of both primary and sterically hindered secondary acceptors, including the important galactose 3-OH acceptors.Oligosaccharides and glycoconjugates incorporating sialic acid residues are ubiquitous in high animals and human beings, and play important roles in a wide variety of biological processes. 1 Over the years considerable efforts have been spent on the development of sialoside donors bearing various leaving groups for efficient installation of α-sialyl linkages, among which 2-sulfide donors of Neu5Ac, ethyl) and S-aryl (phenyl and substituted phenyl) sialosides, have been widely applied. 2 In a previous report, we noted that an N-acetyl-5-N,4-O-oxazolidinone protected 2-phenylthio sialoside donor 1 gave excellent yields and α-selectivities in linking to various primary alkyl and carbohydrate acceptors under the NIS/TfOH in situ activation conditions at −40 °C in dichloromethane (Scheme 1). 3 Importantly, following glycosylation, the oxazolidinone group was readily cleaved under mild conditions leaving the acetamide intact. 3 Similar investigations were also reported by the Takahashi and De Meo groups with N-desacetyl analogs of 1, but harsher conditions were required for cleavage of the oxazolidinone moiety. 4 In an attempt to increase the α-selectivities of the sialylations of 1 with secondary sugar acceptors by means of the nitrile effect, 5 glycosylations promoted by NIS/TfOH were attempted in nitrile solvents at −40 °C. However, no reaction was observed. Noting the work of Oscarson and Lahmann on the reactivity order of various thioglycosides (glucose and galactose), 6,7,8 we turned our attention to the use of more reactive thiosialoside donors, which could possibly be activated in nitrile solvents at low temperature when improved α-selectivities could be anticipated. Here we describe an investigation into the sialylations of 1-adamantanyl thiosialoside donors 2 and 3. The 1-adamantanyl group was chosen because of its greater electron donating properties compared to Oscarson's preferred cyclohexyl group, and the solid (m.p. 99-106°C ) non-volatile nature of 1-adamantanethiol, the precursor for the installation of 1-adamantanylthio leaving group, which reduces the odor problem common to most thiols. 9The penta-acetate derivative 4 10 of neuraminic acid was reacted with 1-adamantanethiol in the presence of BF 3 ·Et 2 O in CH 2 Cl 2 at room temperature to afford 81% of the 1-adamantanyl thiosialoside 5 (Scheme 2). 11 Donor 2 then was derived from 5 in quantitative yield by treatment with i-propenyl acetate catalyzed by CSA at 65 °C (Scheme 2).The preparation of donor 3 started...

An N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donor, the structure of which has been defined through X-ray crystallography, was prepared and tested in couplings to a wide range of acceptors. This donor gives excellent yields and alpha-selectivities in linking with various primary alkyl and carbohydrate acceptors under the N-iodosuccinimide and trifluoromethanesulfonic acid in situ activation method at -40 degrees C in dichloromethane. The favorable affect of the oxazolidinone substructure for alpha-sialylation is illustrated by a comparison study with a N,N-diacetylsialyl donor, which exhibited inferior yields and alpha-selectivities. The sialylation selectivity is independent of the anomeric configuration of the donor, but is highly related to the reaction temperature under the NIS/TfOH activation method. In contrast to the NIS/TfOH method, the Ph2SO/Tf2O promotion gives beta-selective couplings in dichloromethane. The oxazolidinone of the N-acetyl-5-N,4-O-carbonyl protected sialosides, both alpha- and beta-anomers, could be cleaved cleanly by treatment with sodium methoxide under mild conditions without removal of the acetamide.

Two stereocontrolled syntheses of a methyl glycoside of an alternating beta-(1-->4)-beta-(1-->3)-mannohexaose, representative of the mannan from Rhodotorula glutinis, Rhodotorula mucilaginosa, and Leptospira biflexa, are described. Both syntheses employ a combination of 4,6-O-benzylidene- and 4,6-O-p-methoxybenzylidene acetal-protected donors to achieve stereocontrolled formation of the beta-mannoside linkage. The first synthesis is a linear one and proceeds with a high degree of stereocontrol throughout and an overall yield of 1.9%. The second synthesis, a block synthesis, makes use of the coupling of two trisaccharides, resulting in a shorter sequence and an overall yield of 4.4%, despite the poor selectivity in the key step.

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The formation of sialic acid glycosides with a thiosialic acid derivative, diphenyl sulfoxide, and trifluoromethanesulfonic anhydride is reported. With an excess of diphenyl sulfoxide, glycal formation can be completely suppressed and excellent yields are obtained for coupling to a wide range of primary, secondary, and tertiary acceptors.