Synthetic N-Alkylated Iminosugars as New Potential Immunosuppressive Agents

Abstract

The new emerging immunosuppressive effects displayed by iminosugars have not been much investigated so far. Several new N-alkyl dideoxy iminoalditols were designed and synthesized to explore their immunosuppressive effects. These iminosugars inhibited the proliferation of mouse splenocytes and the secretion of both IFN-γ and IL-4, which are the hallmark cytokines of Th1 and Th2 cells, respectively. Some compounds exerted good inhibitory effects. More importantly, the synthetic iminosugars prolonged the allograft survival in the mouse skin transplantation experiment. Our results provide a lead for further elucidation of the structure-activity relationships and modifications of iminosugars for better immunosuppressive agents.

N‐Arylated‐Lactam‐Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation

“…Interestingly, swainsonine, [13] another natural iminosugar, and some synthetic castanospermine analogues [14] with only minor structural differences from castanospermine showed immunostimulating effects. [19] One of the applications of immunosuppressants is the treatment of graft rejection in organ transplantation. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives.…”

“…Instead, the position of the nitrogen atom was modified. [19] These promising results prompted us to undertake further structure-activity relationship (SAR) studies. [23] In this way, iminosugars 3-6 were identified, with small alterations of the polyhydroxylated ring and the alkyl groups on the nitrogen atom.…”

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

“…[31,32] The ozonolysis of the exoglucose, exogalactose, and exomannose alkenes at À78 8C gave the methoxyl acetal lactones, without separation, which were directly subjected to the onepot amination and cyclization tandem reaction, providing N-substituted d-lactams. The N-substituted d-lactams were subsequently reduced by BH 3 -THF, which was followed by catalytic hydrogenolysis to afford N-alkylated 1,5-dideoxy-1,5-iminoalditols 49a, 49b, 50, 51, and 52 (Schemes 5-7).…”

Glycosidase inhibitors: versatile tools in glycobiology

“…Ye and co-workers described 160 new N-alkylated 1,5-dideoxy-1,5-iminopentitols and N-alkylated 1,4-dideoxy-1,4-iminotetritols (e.g. 244, Fig.…”