Synthesis of 6-O-methyl ether of Scorzocreticin and Scorzocreticoside I, metabolites from Sorzonera cretica

Abstract

6-O-methyl ether of racemic scorzocreticin (1a) and its 8-O-β-D-glucoside, scorzocreticoside I (1b), isolated from Greek endemic species Scorzonera cretica have been synthesized. 6,8-Dimethoxy-3-(4-methoxyphenyl)isocoumarin (3) was obtained by reaction of 3,5-dimethoxyhomophthalic acid (2) with 4-methoxy-benzoyl chloride at elevated temperature. Hydrolysis of isocoumarin (3) to keto acid (4) followed reduction and spontaneous cyclodehydration to afford ( ± )-6,8-dimethoxy-3-(4-methoxyphenyl)-3,4-dihydroisocoumarin (5) which was regioselectively demethylated to ( ± )-6-O-methylscorzocreticin (6). Glycosylation of the latter using 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of silver carbonate in quinoline under Koenigs-Knorr conditions afforded 6-methoxy-8-O-glucoside tetraacetate (7) as a 1:1 diastereomeric mixture. Finally, deacetylation of (7) using sodium methoxide afforded the diastereomeric mixture of R and S 6-O-methylscorzocreticin 8-O-glucosides (8). The 6-O-methyl ether of natural scorzocreticoside I (1b) was separated and identified on the basis of sign of optical rotation.

Keywords:

• Isocoumarin glucoside
• Scorzocreticin
• Scorzocreticoside I

Acknowledgements

The author is grateful to Prof. A-L Skaltsounis, School of Pharmacy University of Athens, Greece for providing the original spectra of scorzocreticin and scorzocreticoside I for comparison. The author would also like to thank the Department of Chemistry, Quaid-i-Azam University for financial support.