Protecting Group-Free Glycoligation by the Desulfurative Rearrangement of Allylic Disulfides as a Means of Assembly of Oligosaccharide Mimetics

Abstract

2-(2-Pyridyldithio-3-butenyl) glycosides react with carbohydrate-based thiols in a two step process involving sulfenyl transfer followed by desulfurative 2,3-allylic rearrangement, promoted by either triphenylphosphine or silver nitrate, to give novel saccharide mimetics. In an alternative embodiment of the same chemistry anomeric thiols are coupled with carbohydrates derivatized in the form of 2-(2-pyridyldithio-3-butenyl) ethers. This new method of glycoligation does not require protection of hydroxyl groups and is compatible with the presence of acetamides, azides, trichloroethoxycarbamates, and thioglycosides. Variations on the general theme enable the preparation of mimetics of reducing and non-reducing oligosaccharides as well as of non-glycosidically linked systems.

Synthesis and evaluation of 1,2-trans alkyl galactofuranoside mimetics as mycobacteriostatic agents

“…Compound 1 was described as a mycobacteriostatic agent at a concentration of 0.86 30 mM. 19 This value is far below its Critical Micellar Concentration (CMC) that reaches 6.1 mM.…”

“…Four functional groups were envisioned at the primary position of the galactofuranose, the 6-fluoro, 6-azido, 6-amino and three 30 6-amido. They can be easily introduced thanks to selective nucleophilic attacks of the corresponding nucleophiles on position 6 of the cyclic sulfate 19 (Scheme 1).…”

“…Transesterification of the ester finally gave the targeted octyl β-D-GalfNHAc 13 with 30% yield over two steps. 30 Four biantennary substituents were envisioned at the C-1 position of galactofuranose (C-family 37 was then accomplished in good yield using conditions identical to those employed for the synthesis of 34. 32 Next, glycosylation of alcohols 32, 34 and 38 with 2,3,5,6tetra-O-acyl β-thiogalactofuranoside 39 33 in presence of silver triflate and N-iodosuccinimide gave the corresponding 55 intermediates 40, 41 and 42, respectively (Scheme 4).…”

“…Such Directly Observed Treatment, Short course therapies (DOTS) present multiple shortcomings, like resistance and side-effects. 3 Therefore novel therapeutic approaches, particularly those aimed at exploring new horizons for the 30 development of efficient anti-tuberculosis molecules, are required. The use of poly-and monosaccharides with bactericidal or bacteriostatic activities is nowadays gaining momentum regarding to their natural distribution, in particular in crucial cellular architecture of pathogenic microorganisms.…”

Chemical Diversification of Sialic Acid Glycosides by Stereospecific, Chemoselective Deamination

“…As selective deacetylation of thioacetates in the presence of acetates is facile, thioacetate derivatives such as 28 enable further regioselective diversification at the 5-position by alkylation of thiols and disulfide formation, or by the thiol-ene and yne click [10] and other processes. [11] As 5-mercapto analogues of NeuAc and/or KDN have not previously been accessible through the use of sialyl transferases, [4b, 4c] this example extends the range of accessible α-sialoside derivatives modified at the 5-position and demonstrates the versatility of the chemical approach. Entry 5 (Table 1) illustrates the formation of a 5-fluoro derivative of NeuAc and/or KDN.…”