Synthesis of 1-Deoxy-1-hydroxymethyl- and 1-Deoxy-1-epi-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.

Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds

“…[36] An enzyme inhibition study showed that neither of the compounds had any inhibition toward any glycosidase enzymes (a-mannosidase, a-galactosidase, aglucosidase, b-glucosidase, and b-galactosidase). The effect of compounds 72a and 72b on Con A induced proliferation of splencytes of Swiss albino mice showed that, up to a concentration of 20 mM, compound 72a increased proliferation of Con A-treated cells, with a maximum cell proliferation being observed at 5 mM.…”

Synthesis of Iminosugar‐Containing KRN7000 Analogues

“…[26][27][28] Two castanospermine (an iminosugar) analogues also showed up-regulation of the Th1/Th2 cytokine ratio, with apparent bias towards Th1 cytokines. [29] Based on these observations, and considering that very few examples for iminosugar analogues of GalCer have been reported, [30] it is possible to create new iminosugar-containing compounds and explore their biological activities. Therefore, three KRN7000 analogues were designed, in which the galactose moiety was replaced by iminosugars and the iminosugars were connected with ceramide in different manners (Figure 1, compounds 1 -3).…”

Catechuic acid and ethyl 2,4,5-trihydroxybenzoate from d-glucose

“…20,[40][41][42] While working in the area of carbohydrate chemistry, we have synthesized sugar b-ketoesters and demonstrated their utility in the synthesis of griseolic acid and nojirimycin analogues. [43][44][45][46][47][48][49] We now demonstrate the transformation of sugar b-ketoesters 3a/b to catechuic acid (1) and ethyl 2,4,5-trihydroxybenzoate (2) by emulating the biochemical cascade reactions (vide supra) of intramolecular aldol condensation and enolization that are known from poly-b-ketoesters to phenolic acids/esters. 50 Our results are reported herein.…”