1) The cyclization of phloroglucinol (I) with butyrylacetic acid ethyl ester (II) by means of concentrated sulfuric acid gives 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III), which is condensed with propionyl chloride by means of AlCl3 in nitrobenzene, yielding the 8-propionyl derivative (V). The cyclization of (V) with 3-hydroxy-3-methylbuytyraldehyde dimethylacetal (VI) in refluxing pyridine affords the benzodipyran (VII), which is cyclized again with paraldehyde or acetaldehyde dimethylacetal by means of p-toluenesulfonic acid and trifluoroacetic acid in pyridine at 140 C to give a mixture of the diastereomeric racemates (VIII) and (IX), which are separated by column chromatography. The reduction of racemate (VIII) with NaBH4 /CeCl3 in ethanol yields a new mixture of the racemic hydroxy epimers (X) (racemic calanolide A) and (XI), which are separated by semipreparative HPLC. Racemic calanolide A (X) is finally submitted to optical resolution by semipreparative chiral HPLC.
Calanolide A (I), a compound isolated from the tropical tree Calophyllym lanigerum, was selectively hydrogenated at the 7,8-double bond employing PtO2 poisoned with NH4OH to afford the title compound.