Transformation Into Glycosyl Chlorides

Several routes have been described for the conversion of methyl glycosides into glycosyl bromides or iodides, but they require elevated temperatures incompatible with the presence of interglycosidic bonds. However, methyl glycosides readily 

A 2-(trimethylsilyl)ethyl glycoside is convertible into a glycosyl chloride by treatment with 1,1-dichloromethyl methyl ether in the presence of zinc(II) chloride, tin(IV) chloride, or iron(III) chloride. Normally an a-chloro sugar is the product. If a (3-chloro product is formed first (kinetic product) by participation from a 2-O-substituent, this is rapidly equilibrated into the thermodynamically more stable a product (anomeric effect, Section VI). The transformation is compatible with acetyl, benzoyl, and benzyl protecting groups and most importandy, also with the presence of inter-residue glycosidic bonds 229,230 

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Transformation of 2-deoxysugar derivatives into glycosyl xanthates can be performed by the treatment of O-benzyl-protected hemiacetal derivative with diphe-nylphosphoryl chloride, followed by the reaction with O-ethyl potassium xanthate in the presence of a base (NaOH, PTC reaction or NaH in appropriate organic solvent). High yields and selectivities in such reactions were observed when using sodium hydride in anhydrous THF [401],... 

Glycosyl halides (7a-e) were stereoselectively transformed into l,2-tra s-thio-glycoses by i) (8a-d, 8j) a two-step procedure via the pseudothiourea derivatives [9,10a] the substitution of halide by thiourea is mostly a S l-type reaction since acetylated 1-thio-a-D-mannose (8b) was obtained from acetobromoman-nose (7b) [9cj ii) (8e-i) using thiolates in protic and aprotic solvents [10], or under phase transfer catalysis conditions [11]. Another approach involved the reaction of thioacetic acid with 1,2-trans-per-O-acetylated glycoses catalyzed with zirconium chloride [12]. The 1,2-trans-peracetylated 1-thioglycoses (8e-h) were obtained in high yield. No anomerized products could be detected in these reactions (Fig. 1). 

The synthesis of corresponding pyrimidine nucleosides was not possible by the mercuric chloride method. The syntheses succeeded, however, on application of the Hilbert—Johnson procedure. Tetra-O-acetyl-4-thio-D-ribofuranose was transformed with ethereal hydrogen chloride into the glycosyl chloride derivative 254, and this was directly heated for five days with 2,4-diethoxy-5-methylpyrimidine. The anomeric forms of 4-ethoxy-5-methyl-l-(2,3,5-tri-0-acetyl-4-thio-D-ribofuranosyl)-2(lH)-pyrimidinone obtained could be separated... 

The ability to chemoselectively deprotect pent-4-enyl glycosides opens an avenue for a two-step transformation of NPGs into different glycosyl donors. In this context, NPGs can be transformed [50] into thioglycosides 81 [51,52,53], glycosyl trichloroacetimidates 82 [54], and glycosyl chlorides 83 [55] (O Scheme lie). 

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