Synthesis of anti-HIV lithospermic acid by two diverse strategies.
An efficient and convergent route for the synthesis of the natural product (+)-lithospermic acid, which possesses anti-HIV activity, was accomplished. The (±)-trans-dihydrobenzo[b]furan core therein was prepared by two different strategies. The first strategy involved the use of a palladium-catalyzed annulation to generate an appropriately substituted benzo[b]furan ester followed by a stereoselective reduction of a carbon-carbon double bond with Mg-HgCl(2)-MeOH. The second strategy relied on an aldol condensation between a suitably substituted methyl arylacetate and 3,4-dimethoxybenzaldehyde, followed by cyclization. Finally, a total synthesis of (+)-lithospermic acid was completed via coupling of a trans-dihydrobenzo[b]furan cinnamic acid with an enantiomerically pure methyl lactate.
Department of Chemistry and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
Tirumala G
TG
Varadaraju
Jih Ru
JR
Hwu
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D001547:Benzaldehydes / Q000737:chemistry; D001572:Benzofurans / Q000138:chemical synthesis*; D001688:Biological Products / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D053630:Depsides / Q000138:chemical synthesis*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
D019380:Anti-HIV Agents; D001547:Benzaldehydes; D001572:Benzofurans; D001688:Biological Products; D053630:Depsides; C046833:lithospermic acid; D010165:Palladium; C427725:veratraldehyde