合成路线1

A total synthesis of forskolin has been reported: The intermediate enone (I) [obtained as final product (XVIII) in Delpech, B. et al. Tetrahedron Lett 1996, 37(7): 1015] is reduced with diisobutylaluminum hydride (DIBAL) in hexane/ethyl ether giving the corresponding alcohol (II), which is esterified with N,N-dimethylcarbamoyl chloride and butyllithium in THF yielding the carbamate (III). The reaction of (III) with m-chloroperbenzoic acid (MCPBA) and NaHCO3 in dichloromethane affords the epoxide (IV), which is cleaved with BF3.Et2O in ether affording the trans-diol (V). Elimination of the carbamoyl group of (V) by treatment with LiAlH4 in ethyl ether eliminates also partially the silyl group, so the mixture obtained is resilylated to give the silylated triol (VI). The carbonylation of (VI) with carbonyldiimidazole (CDI) in refluxing toluene yields the cyclic carbonate (VII), which is desilylated by treatment with tetrabutylammonium fluoride (TBAF) in THF to afford the diol (VIII). The Swern oxidation of the primary alcohol of (VIII) gives the corresponding aldehyde (IX), which is condensed with propynyllithium (X) in THF to yield the corresponding addition product (XI). The Collins oxidation of the secondary alcohol of (XI) affords the propargyl ketone (XII), which is cyclized by means of Cs2CO3 in acetonitrile to the naphthopyrone derivative (XIII). The alkylation of (XIII) with lithium divinyl cuprate and BF3.Et2O gives the vinylated compound (XIV), which is treated with NaOH in methanol to eliminate the cyclic carbonate group giving the dihydroxyketone (XVI). Elimination of the acetonide group of (XVI) with p-toluenesulfonic acid in methanol/dichloromethane affords the tetrahydroxyketone (XVII), which is finally selectively acetylated with acetic anhydride and pyridine to forskolin.