Synthesis of 2-Deoxyglycopyranosyl Thioureas from Glycals

Abstract

The reaction of glycals with phenylselenenyl chloride followed by treatment with KNCS lead to 2-deoxy-2-phenylselenoglycopyranosyl isotiocyanates which were further transformed into 2-deoxyglycopyranosyl thioureas.Sugar isothiocyanates are versatile synthetic intermediates in carbohydrate chemistry. By exploiting the strong electrophilic character of the NCS group, a wide variety of other functional groups can be accessed which, in turn, may be subjected to other transformations. The synthesis, chemistry and preparative applications of sugar isothiocyanates have been previously reviewed. 1,2 Glycals are also very versatile intermediates, especially in the synthesis of 2-deoxyglycosides, and different reports have exhaustively covered their synthetic applications. [3][4][5][6][7][8] In particular, the reactions of glycals with electrophilic sulfur and selenium reagents have been studied 9-17 and the factors controlling the stereoselectivity course of the reactions elucidated. 14 By application of these reactions, the introduction of nitrogen in the anomeric position was achieved using phenylselenenyl azide 18 or phenylselenenyl chloride followed by N-glycosidation with bis(trimethylsilyl)uracil 19 allowing the synthesis of 2-deoxyglycosyl azides and 2'-deoxypyranosyl nucleosides, respectively.In this domain we have described 20 the application of glycals as glycosyl isothiocyanate precursors and reported a very convenient route for the simultaneous introduction of the iodo and isothiocyanate functionalities in a sugar molecule. Electrophilic addition of iodine(I) thiocyanate, generated in situ from silica supported KSCN and iodine, to the double bond leads exclusively to trans-2-deoxy-2-iodoglycopyranosyl isothiocyanates. The methodology is relevant for its efficiency, good stereoselectivity and simplicity.We now report the synthesis of 2-deoxy-2-phenylselenoglycopyranosyl isothiocyanates and their transformation into 2-deoxyglycopyranosyl thioureas from glycals. Tri-O-acetyl-D-glucal (1) and -galactal (2) were chosen as starting materials. Reaction of 1 with phenylselenenyl chloride was followed by in situ addition of silica supported KSCN using ether as solvent. The trans addition compounds 3 (a-D-manno) and 4 (b-D-gluco) were isolated in 29 and 33% yield, respectively. However, when 2 was used only the stereoisomer with a-D-talo configuration 5 was obtained in 40% yield. The assignment of the product stereochemistry was based on vicinal proton 3 J H,H and geminal heteronuclear 1 J C1,H1 coupling constants (see Table 2 and 3). Typically, H-1 for the b-gluco product 4 appeared at d = 4.67 as a doublet (J 1,2 = 10.0 Hz), with H-2 appearing at d = 3.15 as a triplet (J 1,2 ªJ 2,3 ). In the case of the a-manno (3) and a-talo (5) isothiocyanates H-1 appeared at d = 5.82 and 5.88 as a doublet (J 1,2 = 1.7 and 1.3 Hz), respectively, and H-2 appeared at d = 3.98 and 3.60 as a doublet of doublets (J 2,3 = 4.4 Hz).In agreement with these assignations is the observed 1 J C1,H1 values that for the a-glycosylpyranosyl isothio...

Thiourea and Selenourea and Their Applications

“…By using the basic reaction, (1-6), (1-1)-thiourea-linked oligosaccharides, thiourea-bridged glycodendrimers, multiple thiourea binding receptors have been prepared (Fig. 1) [28,[93][94][95][96][97][98][99][100][101][102][103].…”

Substituent Dependence of the Diastereofacial Selectivity in Iodination and Bromination of Glycals and Related Cyclic Enol Ethers

“…For example, the electrophilic addition of halogens to cyclic enol ethers has been investigated early by Lemieux and Fraser-Reid who proposed a general mechanism involving the initial formation of carbenium ions which, upon nucleophilic attack by halide ion, give mainly the products of thermodynamic control. Later on, it has been shown that the product formation is under kinetic control and that the stereoselectivity depends on the solvent polarity, − the structure of the enol ether, and the nature of the halogen .…”