Glucopyranosyl isothiocyanate synthesis

Toward a complete synthesis of trehazolin (2), 2,3,4,6-tetra-O-benzyl-1 -deoxy-z-D-glucopyranosyl isothiocyanate (7)52 was brought into reaction with the amines 5 and 374 in the presence of triethylamine to afford the x-D-glucopyranosyl thiourea derivatives 375 or 376, respectively (Scheme 46).38 Subsequent treatment with 2-chloro-3-ethylbenzoxazolium tetrafluoroborate and triethylamine afforded the corresponding amino oxazoline derivatives 377 and 378. Finally, hydrogenation over Pd(OH)2 on carbon afforded trehazolin (2). 

To overcome the problems derived from formation of anomeric mixtures when O-benzylated glycosyl halides are used as precursors, Ledford and Carreira52 have disclosed an elegant synthesis of 2,3,4-tri-O-benzyl-a-D-glucopyranosyl isothiocyanate (10) based on the use of l,6-anhydro-2,3,4-tri-0-benzyl-/t-i)-glucopyranose (9) as the glycosyl donor. Treatment of 9 with tetra-n-butylammonium thiocyanate and boron trifluoride-etherate complex provided 10 in 50% yield with total control of the anomeric configuration (Scheme 5). 

The synthesis of dithioxopyrimidine nucleosides 138 from acetylated /0-D-glucopyranosyl isothiocyanate 89 has been reported by Fuentes and co-workers [149]. J -Glucosylthioamides 137, prepared by reaction of 89 with N-aryl-enaminoesters or enaminones 136 in basic medium, were transformed into glucosyl dithioxopyrimidines nucleosides 138 by treatment with thiophosgene (Scheme 30). The concomitant glycosylamides formation... 

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. ... 

The approach to nucleoside synthesis developed by Ogura et al. (Heterocycles, 911, 8, 125, and earlier references), which involved the reaction of glycosyl isothiocyanates with substituted hydrazines to give thiosemicarbazides which were cyclized with NBS, and finally desulphurized to give the required heterocycle, has now been applied to the synthesis of pyrazolopyrimidine nucleosides derived from D-glucopyranosyl, D-arabinopyranosyl, and d-ribofuranosyl isothiocyanates. Syntheses of nucleoside analogues from reactions of glycosyl isothiocyanates with amino-acids, enamines, and diamines have been summarized. ... 

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