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).
Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, United States.
Jan
J
Hajduch
Ghilsoo
G
Nam
Eun Ju
EJ
Kim
Roland
R
Fröhlich
John A
JA
Hanover
Kenneth L
KL
Kirk
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