A convenient synthesis of the C-1-phosphonate analogue of UDP-GlcNAc and its evaluation as an inhibitor of O-linked GlcNAc transferase (OGT).
The C-1-phosphonate analogue of UDP-GlcNAc has been synthesized using an alpha-configured C-1-aldehyde as a key intermediate. Addition of the anion of diethyl phosphate to the aldehyde produced the hydroxyphosphonate. The configuration of this key intermediate was determined by X-ray crystallography. Deoxygenation, coupling of the resulting phosphonic acid with UMP and deprotection gave the target molecule as a di-sodium salt. This analogue had no detectable activity as an inhibitor of (OGT).
Hajduch
Jan
J
Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, United States.
Nam
Ghilsoo
G
Kim
Eun Ju
EJ
Fröhlich
Roland
R
Hanover
John A
JA
Kirk
Kenneth L
KL
D000447:Aldehydes; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors*; D010755:Organophosphates; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000138:chemical synthesis* / Q000494:pharmacology
D000447:Aldehydes; D010755:Organophosphates; D063065:Organophosphonates; D014537:Uridine Diphosphate N-Acetylglucosamine; C034789:diethyl phosphate; D017351:N-Acetylglucosaminyltransferases