Syntheses of mycophenolic acid and its analogs by palladium methodology

Syntheses of mycophenolic acid (MPA, 1) and its analogs were carried out us ing palladium-catalyzed Heck carbonylation and olefination. Thus, the react ion of 2-bromo-3,5-dimethoxybenzyl alcohol (4) in toluene under carbon mono xide at 180 degreesC in the presence of palladium catalyst using sodium car bonate as a base gave 5,7-dimethoxyphthalide (5) in 88% yield. The phthalid e 7 was converted to 6-iodo-5,7-dimethoxy-4-methylphthalide (8). Reaction o f aromatic iodide 8 with isoprene and dimethyl malonate in the presence of palladium(0) catalyst gave the three component coupling product 9, which wa s converted into 1 in three steps. 4-NorMPA (16) and 4-homoMPA (22) were sy nthesized similarly.