Sugar isothiocyanates synthesis

This article collates information on the reactivity of sugar isothiocyanates and isomeric thiocyanates, and illustrates some of the chemical properties that have contributed to the synthesis of nucleoside analogs,1719 and thio and deoxy sugars. 

The classical, Fischer7 synthesis of sugar isothiocyanates involves treatment of an acylated glycosyl halide with an inorganic thiocyanate in a polar solvent. Depending on the reactivity of the halide and the reaction conditions, either a thiocyanate or an isothiocyanate is formed directly. 

Sugar Isothiocyanates as Intermediates in the Synthesis of Nucleoside Analogs... 

Fernandez-Bolanos JG, Lopez 0, Maya I (2003) Synthesis of O-unprotected sugar isothiocyanates and their transformation into thioureas and cyclic isoureas. In Pan-dalai S (ed) Recent Developments in Carhohydrate Research, Transworld Research Network, Trivandrum, India, p 81... 

The ImCSIm-method has been used, for instance, in the synthesis of isothiocyanates containing steroid, sugar, and alkaloid components ... 

Guthrie and Irvine35 also developed an original synthesis of unsaturated isothiocyanates, starting from a mixture of the unsaturated azido sugars 15... 

In an article that collates information not extensively treated before, Z. J. Witczak (West Lafayette) describes the synthesis, chemistry, and preparative applications of monosaccharide thiocyanates and isothiocyanates the thiocyanate anion is an ambident nucleophile of great synthetic versatility in approaches to nucleoside analogs and to thio and deoxy sugars. 

Sugar derivatives having isothiocyanate groups on the various carbon atoms were used for the synthesis of trehazoline and its analogues. Thus, the glycosyl isocyanate, where the isothiocyanate group is at the anomeric center, as required for the synthesis of trehazolin 2, was readily synthesized by reaction of the glycosyl donor 6 with a metal isothiocyanate (Scheme 2).23... 

Thioamides can serve as surrogates for isothiocyanates in the Marckwald synthesis. For example, reaction of a-amino acetals 1278 with thioamides 1277 in the presence of HgClz affords amidine intermediates, which cyclize to form imidazoles under acidic conditions. This method has been applied to synthesize a variety of sugar imidazoles (Scheme 324) <2005HCA10, 2004HCA3035, 2004HCA719, 2000TA435>. 

In this work, we will describe the use of sugar-derived isothiocyanates in the stereocontrolled synthesis of heterocychc derivatives, such as 1,3-oxazohdine- and l,3-oxazinane-2-thiones (5- and 6-membered cyclic thiocar-bamates, respectively), 2-amino-2-oxazolines (5-membered cyclic isoureas), nucleosides, spiroglycosides and spironucleosides, and compounds that are simultaneously pseudo-C- and N-nucleosides. 

The equilibrium mixture of these two compounds can be directly used for the preparation of sugar-derived thioureas by coupling with alkyl and aryl amines [47]. This was the first example in the literature of a thio carbamate acting as a latent isothiocyanate for the synthesis of thioureas. 

The synthesis of p-o-glucopyranosyl-thioureas has been reported. N -Glucosylated sugar urea and thiourea derivatives such as 42 were synthesized by PhsP-induced condensation of the corresponding protected 6-azido-sugar with tetra-O-acetyl-p-D-glucopyranosyl isothiocyanate followed by either hydrolysis (HOAc, H2O) or thiolysis (H2S, silica gel), respectively, then deprotection. Acetylation of such doubly substituted thiourea derivatives led to various re-gioisomeric N- and S-acetylated derivatives. ... 

---