Abstract
In this thesis, asymmetric syntheses of methyl lactate and its antipode has been discussed. Application of these chiral synthons culminated in the asymmetric syntheses of both the antipodes of polymethylated rosmarinic acid, salvianolic acid A, salvianolic acid C, and salvianolic acid D. In addition, a modular, flexible, and convergent route to the heptamethyl lithospermic acid has been described. The heptamethyl lithospermic acid was accomplished in 5 steps from the known compounds in 28% overall yield. The trans-dihydrobenzofuran core of heptamethyl lithospermic acid was achieved by stereoselective reduction of benzo[b]furan with magnesium in methanol. Furthermore, an alternative method for the synthesis of trans-cinnamic acid derivative has been devised and can be applicable for enantioselective synthesis of lithospermic acid. The biological activity of polymethylated caffeic acids against HIV-1 virus replication was evaluated. Among them, polymethylated (+)-rosmarinic acid and (±)-salvianolic acid C were found to inhibit the replication of HIV-1RTMF (AZT-resistant) virus with IC50 values of 34 µM and 50 µM respectively. Also, this thesis presents the total synthesis of polyphenolic acids which exploits tert-butyldimethylsilyl (SiMe2t-Bu) as an ideal protecting group. In order to prove that, total synthesis of (±)-rosmarinic acid was completed in 7 steps and 42% overall yield from caffeic acid. Furthermore, efficient and flexible routes were established for the syntheses of orthogonally protected skeleton of oresbiusin, salvianolic acid C, and salvianolic acid D.