合成路线1

An enantioselective total synthesis of (+)-calanolide A has been reported: The silylation of 2'-hydroxy-4',6'-dimethoxybutyrophenone (I) with TIPS-Cl by means of benzylltriethylammonium chloride and NaOH in benzene gives the silyl ether (II), which is demethylated with BCl3 in dichloromethane yielding 2'-hydroxy-4'-methoxy-6'-(triisopropylsilyloxy)butyrophenone (III). The Wittig condensation of (III) with the phosphorane (IV) in N,N-diethylaniline with simultaneous cyclization, affords the benzopyranone (V), which is submitted to a Friedel-Crafts condensation with the acyl chloride (VI) by means of SnCl4 in dichloromethane to provide the 8-acylbenzopyranone (VII). The desilylation of (VII) by means of TBAF in THF/dichloromethane gives the 5-hydroxy compound (VIII) which is submitted to a propargylation with alcohol (IX) and DBU and then to a Claisen rearrangement with N,N-diethylaniline affording the pyrano-benzopyran (X). Demethylation of (X) with MgI2 in refluxing benzene gives the phenol (XI), which is submitted to a (-)-quinine-catalyzed asymmetric intramolecular oxo-Michael addition in chlorobenzene yielding an 80:20 mixture of the chiral cis- and trans-benzotripyrans (XII) (94% ee) and (XIII), respectively. Since the desired compound is the minor component (XIII), the preceding mixture is treated with MgI2 in refluxing benzene to afford an equilibrated 50:50 mixture that is separated by chromatography, and the undesired cis-isomer can be recycled by repeating the MgI2 treatment. The enantiomerically rich trans-isomer (XIII) is finally reduced with LiAlH(Ot-Bu)3 in THF.