SYNTHETIC ROUTES FROM PAROMAMINE TO THE OCTODIOSE-CONTAINING PSEUDODISACCHARIDE PRESENT IN (OXY)APRAMYCIN

Article abstract of DOI:10.1016/0008-6215(84)85280-5

The synthesis of a 4-O-(2-amino-2-deoxyoctodiosyl)-2-deoxystreptamine, the first synthetic analog of the unusual pseudodisaccharide present in (oxy)apramycin was accomplished, starting from paromamine, by a two-carbon chain-elongation and a stereoselective cis-hydroxylation of the resulting E-unsaturated octuronate to give either ethyl <1-N-5,6-di-O-benzoyl-2-deoxy-1,3-di-N-p-tolylsulfonylstreptamin-4-yl> 3,4-di-O-benzoyl-2-deoxy-2-p-tolylsulfonamido-D-threo-α-D-gluco- (12) or -L-threo-α-D-gluco-octo-1,5-pyranosid> uronate.Mehtoxide-mediated deacylation of 12 afforded in one step a bicyclic, trans-decalone-like urono-8',4'-lactone (14) that was highly sensitive to acid-catalyzed alcoholysis and had properties in sharp contrast to those of D-glucurono-6,3-lactone.Partial reduction of lactone 14 or of the corresponding methyl octuronate 12 with lithium aluminum hydride at low temperature gave the expected α-D-threo-D-gluco-octodialdo-1,5-pyranoside-8,4-pyranose, which was methanolyzed and N-detosylated to afford the free pseudodisaccharide 1-(2-deoxystreptamin-4-yl) 8-methyl (8R,S)-2-amino-2-deoxy-α-D-threo-D-gluco-octodialdo-1,5:8,4-dipyranodioside.All of the octodiose derivatives were found to adopt a rigid, dipyranoid structure.