Chemo-enzymatic synthesis of 1,4-oxazepanyl sugar as potent inhibitor of chitinase.
N-acetyl glucosamine 1 is selectively converted into 2 without protection of the other hydroxyl groups by allylation of the anomeric alkoxide in N,N-dimethylformamide containing lithium bromide. We use cell density cultures to produce the allylated derivative of penta-N-acetyl-chitopentaose by using 2 as the initial acceptor for the synthesis of 3 in vivo. Upon periodate oxidation, 3 is transferred to 4. Compound 4 is quickly subjected to sodium borohydride reduction and NH3 amination, which afforded the target compound 5. In 5-binding chitinase assay, it indicates that the chitinase is obviously inactivated by 5 with IC50 = 4.7 micromol/L.
Huang
Gang-Liang
GL
School of Life Science, Shandong University, Jinan City 250100, China.
Zhang
Da-Wei
DW
Zhao
Hong-Juan
HJ
Zhang
Hou-Cheng
HC
Wang
Peng-George
PG
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002688:Chitinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005960:Glucosides; D006027:Glycosides; D009844:Oligosaccharides; C511150:penta-N-acetyl-chitopentaose; D002688:Chitinases