Glycomimetics: A Versatile de Novo Synthesis of β-1-C-Aryl-deoxymannojirimycin Analogues
journal contributionposted on 22.08.1997, 00:00 by Carl R. Johnson, Brian A. Johns
The synthesis of 11 β-1-C-aryl-deoxymannojirimycin analogues using a versatile de novo strategy is described. The origins of this report are derived from several recent developments in the area of C1-substituted glycomimetic polyhydroxylated piperidines. This study is designed as a structure−activity comparison to explore the effects of aryl substitution on the ability of the title compounds to inhibit glycosidase enzymes. The polyhydroxylated piperidine ring was constructed using vinyl bromide 10, which was synthesized in six steps from the bromobenzene microbial oxidation metabolite bromo diol 9. A palladium-catalyzed Suzuki cross-coupling of vinyl bromide 10 and the corresponding arylboronic acid served as the key pseudoanomeric carbon−carbon bond-forming step. Ozonolysis and selective reduction of the resultant carbonyl functions followed by reductive amination served to produce the azasugar ring. The complete NMR analysis of the resultant piperidine ring stereochemistry is also discussed. Fully deprotected β-1-C-aryl-deoxymannojirimycin analogues 8·HCl were obtained upon acidic deprotection.
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analoguearylboronic acidvinyl bromide 10carbonyl functionstitle compoundsglycomimetic polyhydroxylated piperidinesazasugar ringpiperidine ring stereochemistryoxidation metabolite bromo diol 9acidic deprotectionreductive aminationaryl substitutionNovo Synthesispolyhydroxylated piperidine ringC 1glycosidase enzymesNMR analysis