Regioselective synthesis of cyclodextrin mono-substituted conjugates of non-steroidal anti-inflammatory drugs at C-2 secondary hydroxyl by protease in non-aqueous media.
Three beta-cyclodextrin (beta-CD) conjugates of non-steroidal anti-inflammatory drugs were synthesized by enzymatic methods. Transesterification of beta-CD with vinyl ester of indomethacin, ketoprofen and etodolac was performed by the catalysis of alkaline protease from Bacillus subtilis in anhydrous DMF for 3 days. The drug molecules were selectively conjugated onto one of the secondary hydroxyl groups of beta-CD through ester-linkage to improve their poor water solubility and absorption characteristics. The products were characterized by ESI-MS, (1)H NMR and (13)C NMR. The structures of products with monoacylation occurring at the C-2 secondary hydroxyl groups of beta-CD were confirmed.
Wang
Na
N
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China.
Wu
Qi
Q
Xiao
Yong Mei
YM
Chen
Chun Xiu
CX
Lin
Xian Fu
XF
D000215:Acylation; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010447:Peptide Hydrolases / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D010447:Peptide Hydrolases