SYNTHESIS OF MYCOPHENOLIC ACID β-D-GLUCURONIDE AND ITS ANTITUMOR ACTIVITY

Mycophenolic acid β-D-glucuronide [V] wsa synthesized by KOENIG'S KNORR reaction from methyl mycophenolate [II] and methyl-(tri-O-acetyl-α-D-glucopyranosyl bromide)-uronate [VII]. Hydrolysis of mycophenolic acid β-D-glucuronide by β-glucuronidase liberates mycophenolic acid and glucuronic acid. Upon acid hydrolysis, the T-lactone derivative is formed instead of mycophenolic acid. Mycophenolic acid β-D-glucuronide shows significant antitumor activity against the Ehrlich solid tumor, although it was without effect on nucleic acids synthesis of L-5178 Y cells and the growth of any microorganisms tested. The acute toxicity is very low ; mice tolerate 2, 000 mg/kg intraperitoneal injection.