Synthesis and biological activities of (4,6-di-O-phosphonato-beta-D-mannopyranosyl)-methylphosphonate as an analogue of 1L-myo-inositol 1,4,5-trisphosphate.
The synthesis of the alpha and beta anomers of the title compound (1) was accomplished from D-mannose. In the key step, the phosphonate analogues of the mannopyranosyl phosphates were prepared by a direct Wadsworth-Emmons condensation of a protected mannose derivative (8) with tetraethyl methylenebisphosphonate under two-phase conditions. In vitro bioassays have shown that the beta anomer (1a) is a potent inhibitor of Ins(1,4,5)P3 3-kinase and inhibits other enzymes.
Chung
S K
SK
Department of Chemistry, Pohang Institute of Science & Technology, Korea.
Moon
S H
SH
D000818:Animals; D002417:Cattle; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives*; D000072181:Inositol Polyphosphate 5-Phosphatases; D008099:Liver / Q000201:enzymology; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects*; D051381:Rats; D011994:Recombinant Proteins / Q000187:drug effects; D013237:Stereoisomerism; D013737:Testis / Q000201:enzymology
C088899:(4,6-di-O-phosphonatomannopyranosyl)methylphosphonate; D063065:Organophosphonates; D011994:Recombinant Proteins; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D008358:Mannose