Synthesis of 1-Deoxy-1-hydroxymethyl- and 1-Deoxy-1-<i>epi</i>-hydroxymethyl Castanospermine as New Potential Immunomodulating Agents

Abstract

Two new C-1 epimeric hydroxymethyl castanospermine congeners 2a and 2b, synthesized by stereocontrolled intramolecular double reductive amination of D-glucose derived beta-keto ester as a key step, showed impressive immuno-potentiating property. The bioactivity was mediated through up-regulation of T(H1)/T(H2) cytokine ratio. The finding suggested that immunmodulatory activity of polyhydroxylated indolizidine alkaloids can be tuned by minor structural/stereochemical alterations.