Dihydrocalanolide A-(+), (+)-Dihydrocalanolide A, NSC-678323

Chemical Name: (10R,11S,12S)-12-Hydroxy-6,6,10,11-tetramethyl-4-propyl-7,8,11,12-tetrahydro-2H,6H,10H-benzo[1,2-b:3,4-b':5,6-b'']tripyran-2-one
CAS No. 183904-53-2
项目整合开发状态: Preclinical
项目研究机构: National Cancer Institute (Originator)
合成路线: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.

合成路线: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.