Methyl 1-deoxynojirimycin derivatives

Of nearly 50 iminosugars probed for antiHIV activity [183], five were active at subcytotoxic levels. In particular, the a-glucosidase inhibitors 1-deoxynojirimycin 2 and the plant alkaloid castanospermine 4 were confirmed to be active at concentrations between 0.1 and 0.5 mg/ml. Even more pronounced were the activities of 1-deoxynojirimycin derivatives with enhanced lipophilic character such as V-methyl- 70, V-ethyl- 71 and, in particular, V-butyl-1-deoxynojirimycin 72 in the same concentration range [183,186]. 

From the long list of glycoproteins reported to associate with CNX/CRT, it may be concluded that most glycoproteins, irrespective of their final intracellular destination or soluble or membrane-bound status, transiently interact with CNX and CRT in mammalian cells (83-100). In all cases tested, addition of GI/GII inhibitors (such as castanospermine and 1-deoxynojirimycin or its /V-methyl or /V-butyl derivatives) prevented not only interaction of CNX/CRT with folding glycoproteins in mammalian cells but also dissociation of already formed glycoprotein-CNX/CRT complexes (55, 82-96, 101). Furthermore, no glycoprotein-CNX/CRT interaction was observed in GI- or Gll-dehcient cell lines (89, 102). As expected from differences observed in mammalian... 

The inseparable isomeric nitrones formed by reaction of deoxynojirimycin (DNJ) derivative 63 with dimethyldioxirane, gave the 1,3-dipolar cycloadducts 64 and 65 on reaction with trichloroacetonitrile (Scheme 12). The P-l-C-substituted-DNJ derivative 66 was obtained from the reaction of a related nitrone with methyl 3-butenoate under high pressure (15 kbar), but overall the access to this... 

Deoxymannojirimycin has been synthesized with excellent diastereoselec-tivity in a process based upon a palladium(II)-catalysed cyclization of an allylic alcohol 62 derived from D-mannitol. C-6 Homologues of 1-deoxynojirimycin and 1-deoxy-L-idonojirimycin (l,5,6-trideoxy-l,5-imino-D-gf/Mco- and -h-ido-heptitols) have also been prepared using palladium chemistry. In these reports the protected aminohex-l-enitol 63, derived from methyl a-D-glucopyranoside, was amino-carbonylated in the presence of palladium(II) chloride to afford a mixture of cyclized products whose composition was dependent upon the reaction conditions utilized. Two of these products, 64 and 65, were reductively transformed into the DNJ and 1-deoxy-L-idonojirimydn homolgues respectively 58,59... 

The tunicamine derivative 33 has been synthesized from 2-azido-2-deoxy-D-galactose. L-Sorbose has been used as a substrate for symthesizing 1-deoxynojirimycin via the azide 34, which was converted to the antibiotic in a one-pot reaction. Another synthesis employs methyl... 

AT-Methyl- and -butyl-derivatives of deoxynojirimycin, l,4-dideoxy-l,4-imino-D-arabinitol and 2,S-dideoxy-2,5-imino-D-mannitol have been studied by NMR spectroscopy to provide data for determining a conformational basis for the inhibition of glycosidase and HIV-1 replication activity by these types of compounds. ... 

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