Modifications at C-5 and Substitution for the Ring Oxygen

The C-5-O-trifyl group can be displaced by iodide that in turn can be displaced by azide, with overall retention of the configuration (reaction 4.119) to give 5-amino-5-deoxy-D-glucose and the synthesis of nojirimycin [112]. Nojirimycin readily looses water, forming the imine that can be reduced with sodium borohydride to give the stable product, dihydronojirimycin (reaction 4.119). 

Starting with the 1,2-0-isopropylidene-a-D-glucofiiranoside, the C-6 hydroxyl can be tritylated and the C-5 hydroxyl carbon oxidized with acetic anhydride in DMSO to give a 75% yield of the 5-keto compound. The oxime of the keto compound can be formed and reduced with lithium aluminum hydride in diethyl ether [113]. Two C-5 diastereoisomers are formed in a ratio of 9 1, with the D-isomer predominating (reaction 4.120). 

Nojirimycin is a naturally occurring antibiotic that is elaborated by several strains of Streptomyces. It is relatively unstable and must be isolated as the stable bisulfite adduct. It can also be stabilized by reduction with sodium borohydride to give dihydronojirimycin which retains its full antibiotic activity. 

The iodo group of l,2-isopropylidene-5-iodo-6-0-tiityl a-D-glucofiiranoside can also be displaced by thioacetate to form the 5-acetylthio derivative [114]. After the removal of the protecting groups, 5-deoxy-5-thio-D-glucopyranose is obtained (reaction 4.121). 

5-Thio-D-xylose has been prepared in a similar manner [112]. 1,2-0-Isopropy-lidene-5-O-tosyl a-D-xylofiiranoside was reacted with the sodium salt of ben-zylthio alcohol, followed by reaction with sodium amide and acid (reaction 4.122). 

---