合成路线1

3) Synthesis of ent-Calanolide A, (-)-calanolide A: The Clemensen reduction of 5,7-dihydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-one (XXI) with Zn/HCl in methanol gives 5,7-dihydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran (XXII), which is condensed with methyl 2-hexynoate (XXIII) using the palladium catalyst Pd2dba3 to yield dihydrobenzodipyran (XXIV). The regio- and enantioselective allylic alkylation of (XXIV) with 2-methyl-2(E)-butenyl carbonate (XXV) catalyzed by Pd2dba3 using a chiral ligand affords the chiral dihydrobenzodipyran ether (XXVI), which is dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dioxane to (XXVII). The chemoselective hydroboration of (XXVII) with 9-BBN and H2O2 gives the alcohol (XXVIII) with high diastereomeric selectivity. The Dess-Martin oxidation of (XXVIII) yields the expected aldehyde (XXIX), which is cyclized to (10S,11R,12R)-benzotripyran (XXX) (ent-calanolide B). Finally, this compound is converted into ent-calanolide A by inversion of the C-12 hydroxy group carried out with a modified Mitsunobu reaction with dimethyl azodicarboxylate (DEAD)/trimethylphosphine/chloroacetic acid in toluene/THF, followed by treatment with NH4OH in methanol. The authors indicate that Calanolide A can be synthesized in the same way by simply using the mirror image of the chiral ligand in the addition of carbonate (XXV) to dihydrobenzodipyran (XXIV).