A novel stereoselective synthesis of (-)-quinic acid starting from the naturally abundant (-)-shildmic acid

作者：Zhang, Wei; Zhu, Xing-Liang; Ding, Wei; Shi, Xiao-Xin^*

来源：Tetrahedron: Asymmetry , 2015, 26(23): 1375-1381.

DOI：10.1016/j.tetasy.2015.10.008

• OSELTAMIVIR PHOSPHATE TAMIFLU
• QUINIC ACID
• SHIKIMIC ACID
• STEREOSPECIFIC SYNTHESIS
• ASYMMETRIC-SYNTHESIS
• D-(-)-QUINIC ACID
• DERIVATIVES
• EFFICIENT
• DIHYDROXYLATION
• CONSTITUENTS

A new stereoselective synthesis of (-)-quinic acid from the naturally abundant (-)-shildmic acid is described. Ethyl shikimate 2 was first prepared in 97% yield via esterification of (-)-shildmic acid according to a previous report. Ester 2 was then transformed into an epimeric mixture of 3,4-O-benzylidene shikimate 3, which was directly converted into compound 4 in 90% yield (over 2 steps from ester 2) via an NBS-mediated acetal ring-opening reaction. Acetylization of the hydroxyl group at the C-5 position of compound 4 gave compound 5 in 98% yield. Compound 5 was transformed into compound 6 in 91% yield via a highly stereoselective Ru-catalyzed dihydroxylation. Subsequently, compound 6 was converted into epoxide 7 in 82% yield via an intramolecular S(N)2 type substitution. A regioselective epoxide-opening of compound 7 by PPh3-I-2 complex furnished an iodo compound 8 in 79% yield. Removal of the iodine atom in compound 8 by Pd/C-catalyzed hydrogenation produced compound 9 in 92% yield. Methanolysis of compound 9 gave methyl quinate 10 in 92% yield. Finally, hydrolysis of compound 10 afforded the targeted compound (-)-quinic acid 1 in 90% yield. The title compound (-)-quinic acid I was stereoselectively synthesized through 10 steps starting from (-)-shildmic acid in 38% overall yield.

• 出版日期2015-12-15
• 单位华东理工大学