Synthesis and Analgesic Activity Assessment of Furanolabdanoid Conjugates with Glucuronic Acid

• Published in: Chemistry of natural compounds Vol. 56; no. 4; pp. 678 - 687
• Main Authors: Brusentseva, O. I., Kharitonov, Yu. V., Dolgikh, M. P., Tolstikova, T. G., Shul’ts, E. E.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2020; Springer; Springer Nature B.V
• Subjects: Alkynes; Analgesics; Chemical activity; Cycloaddition; Irritation; Medicine; Organic Chemistry; Pharmacy; Plant Sciences; Trienes; diterpenoids; analgesic activity; CuAAC reaction; glycoconjugate; azides; glucuronic acid
• ISSN: 0009-3130; 1573-8388
• DOI: 10.1007/s10600-020-03119-7

Phlomisoic acid reacted with methyl-1-deoxy-2,3,4-tri-
O
-acetyl-1-bromo-
α
-D-glucopyranuronate to form the 18-
O
-
β
-D-(glucuronopyranoside)-6′-
O
-methyl ester of 15,16-epoxylabda-8(9),13,14-triene. Reductive amination of methyl 16-formyl-15,16-epoxylabda-8(9),13,14-trienoate or this
β
-D-glucuronopyranoside of 16-formyl-15,16-epoxylabda-8(9),13,14-triene by propargylamine in the presence of NaBH
4
gave the corresponding 16-propargylaminomethyl-15,16-epoxylabda-8(9),13,14-trienes. Copper-catalyzed azide-alkyne cycloaddition of the new terpenoid alkynes and the propargylamide of phlomisoic acid with methyl 1-deoxy-2,3,4-tri-
O
-acetyl-1-azido-
α
-D-glucopyranuronate synthesized the corresponding labdanoid glucuronides and diglucuronide. Selective screening of the labdanoid triazolylglucuronides identified compounds with analgesic activity in chemical and thermal irritation tests.