合成路线1

The cyclization of phloroglucinol (I) with 3-oxohexanoic acid methyl ester (II) by means of conc. sulfuric acid gives the benzopyranone (III), which is acylated with 2-methyl-2-butenoyl chloride (IV) and AlCl3 in dichloroethane to yield the 5-hydroxy-7-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (V). This compound, without isolation, rearranges under the reaction conditions to afford 5,7-dihydroxy-8-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (VI). The cyclization of (VI) with 3-methyl-2-butenal (VII) in refluxing pyridine provides the benzo-tripyran-2,12-dione derivative (VIII) -alternatively, conversion of (VI) into (VIII) can be performed by first cyclization of (VI) by means of TEA to furnish compound (IX), which is then subjected to cyclization with 3-methyl-2-butenal (VII)-. Finally, reduction of (VIII) with LiAlH(OBu)3 in THF provides the target calanolide A.