Synthesis of Racemic Amino Carba-sugars

Carba-glycosylamines [2,3,4-trihydroxy-5-(hydroxymethyl)-1 -cyclohex-ylamine] and related compounds are well known to exist as components of the antibiotic validamycin complex and carba-oligosaccharidic alpha amylase inhibitors.  

Microbial degradation of validamycin A (8) with a cell suspension of Pseudomonas dentrificans afforded validamine (202) and valienamine (203). Hydrogenolysis of validamycin B, followed by acid hydrolysis, yielded hydroxy validamine (204). Valiolamine (205) was isolated and shown to be a component of validamycin G. ° Biosynthesis of these carba-glycosylamines was extensively studied, and the intramolecular aldol addition of the 

6-diketose derived from sedoheptulose 7-phosphate was presumed to be involved in the formation of the key intermediate, the branched-chain ino-sose derivatives 203, 204, and 205. Compounds 202, 203, and 205 possess detectable inhibitory activity against some hydrolases. Chemical modification of205, the most potent among them, provided some inhibitors strong enough to be applicable to clinical treatment of diabetes. 

The bromo methyl ester (212) formed by treatment of 30 with hydrogen bromide in acetic acid could also serve as a precursor to validamine.  

The 2-deoxy derivative (215) of 202 was prepared from the diacetate 213, obtained by debromination of 34, following a similar sequence starting from the dibromide 214. 

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