Iminosugar
Animinosugar,also known as animinosaccharide,is anyanalogof asugarwhere anitrogenatom has replaced theoxygenatom in the ring of the structure.
Iminosugars are common components of plants and may be responsible for some of their medicinal properties.[1]The first iminosugar to be isolated from a natural source,1-deoxynojirimycin(DNJ), found inMulberry,was reported in 1976, but few others were discovered until many years later.[2]
In terms of biochemical activity for medicinal applications, DNJ and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB, another early example of this class of compounds) areAlpha -glucosidase inhibitorsand were shown to have anti-diabetic and anti-viral activity. DNJ was modified to produce two derivatives now used as medicines,N-hydroxyethyl-DNJ (miglitol) for diabetes andN-butyl-DNJ (miglustat) forGaucher's disease.Anti-cancer and anti-viral activity was subsequently observed forswainsonine—amannoseanalogue—andcastanospermine—aglucoseanalogue—in the 1980s.[3]More than 200 have now been reported from plants and micro-organisms. Although the early compounds had biological activities due to glycosidase inhibition, an increasing number are being shown to have therapeutic potential without being glycosidase inhibitors and may interact with sugar receptors in the body or chaperone deficient enzymes such as inlysosomal storage disordersor incystic fibrosis.[2]
Structure and stability
[edit]The nitrogen of the iminosugar ring structure is ahemiaminallinkage, which, like thehemiacetalof a regular glycoside, is unstable. The 1-deoxy analogs of iminosugars areC-glycosides,with the nitrogen as part of an ordinary amine linkage. Theirpiperidine,pyrrolidine,or similar rings are stable.[4]
See also
[edit]References
[edit]- ^Watson AA, Fleet GW, Asano N, Molyneux RJ, Nash RJ (2001)."Polyhydroxylated alkaloids—natural occurrence and therapeutic applications".Phytochemistry.56(3):265–95.doi:10.1016/S0031-9422(00)00451-9.PMID11243453.
- ^abNash RJ, Kato A, Yu CY, Fleet GW (2011). "Iminosugars as therapeutic agents: recent advances and promising trends".Future Med Chem.3(12):1513–21.doi:10.4155/fmc.11.117.PMID21882944.
- ^Asano N, Nash RJ, Molyneux RJ, Fleet GW (2000). "Nitrogen-in-the-Ring Sugar Mimetics: Natural Occurrence, Biological Activity and Prospects for Therapeutic Application".Tetrahedron Asymmetry.11:1645–1680.doi:10.1016/S0957-4166(00)00113-0.
- ^Compain P, Chagnault V, Martin OR (2009). "Tactics and strategies for the synthesis of iminosugar C-glycosides: a review".Tetrahedron: Asymmetry.20:672–711.doi:10.1016/j.tetasy.2009.03.031.
