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Diels-Alder reaction of 2-chloro-1,3-butadiene with anthracene-1,4,9,10-tetraone was found to occur exclusively at the external(C2,3) double bond, giving the adduct in an excellent yield. The adduct was readily converted to the 4-demethoxyanthracyclinone intermediate, (±)-7-deoxy-4-demethoxydaunomycinone, by way of 5,12-dihydroxy-l,2,3,4-tetrahydronaphthacene-2,6,11-trione.

The title reagent was found to effect the glycosidation of (+)-4-demethoxyanthracyclinones with N-trifluoroacetyl-1,4-di-O-p-nitrobenzoyl-L-daunosamine, giving the ot-glycosides in 99% yields. Sequential deprotections of the glycoside readily afforded optically pure (+)-4-demethoxydaunorubicin.

Optically pure (+)-4-demethoxydaunorubicin has been prepared by a novel glycosidation reaction of (+)-4-demethoxydaunomycinone with (−)-3-N-trifluoroacetyl-1,4-bis(O-p-nitrobenzoyl)-L-daunosamine in the presence of trimethylsilyl triflate, followed by sequential O- and N-deprotection reactions. Total synthesis of optically pure (+)-4-demethoxyadriamycin has been also accomplished by two different synthetic schemes, starting from (+)-4-demethoxydaunorubicin or by way of (+)-3′-N-trifluoroacetyl-4-demethoxyadriamycin. (+)-4-Demethoxyadriamycin prepared by our hands was fully characterized by its spectral properties.

Diels-Alder reaction of 2-chloro-1,3-butadiene with anthracene-1,4,9,10-tetrone was found to occur exclusively at the external (C2,3) double bond, giving the adduct in an excellent yield. The adduct was elaborated to 5,12-dihydroxy-1,2,3,4-tetrahydro-2,6,11-naphthacenetrione. The conventional cyanohydrin formation of this sample followed by acid hydrolysis gave (±)-2,5,12-trihydroxy-6,11-dioxo-1,2,3,4-tetrahydro-2-naphthacenecarboxylic acid. The racemic acid was found to be cleanly resolved by forming a salt with (−)-N-methylephedrine, furnishing optically pure (R)-carboxylic acid. Successive treatments of the (R)-carboxylic acid with N,N′-carbonyldiimidazole and methylmagnesium bromide in the presence of trimethylsilyl triflate readily produced optically pure (R)-(−)-7-deoxy-4-demethoxydaunomycinone, the key synthetic intermediate of (+)-4-demethoxydaunomycinone.

(±)-2,5,12-Trihydroxy-1,2,3,4-tetrahydronaphthacene-6,11-dione-2-carboxylic acid was found to readily afford the racemic title compound by successive treatments with N,N′-carbonyldiimidazole and methylmagnesium bromide in the presence of trimethylsilyl triflate. The same reaction scheme could also furnish the optically pure title compound from the (R)-carboxylic acid produced by the optical resolution.

The title reagent was found to effect the glycosidation of (+)-4-demethoxyanthracyclinones with N-trifluoroacetyl-1,4-di-O-p-nitrobenzoyl-L-daunosamine, giving the ot-glycosides in 99% yields. Sequential deprotections of the glycoside readily afforded optically pure (+)-4-demethoxydaunorubicin.

Diels-Alder reaction of 2-chloro-1,3-butadiene with anthracene-1,4,9,10-tetrone was found to occur exclusively at the external (C2,3) double bond, giving the adduct in an excellent yield. The adduct was elaborated to 5,12-dihydroxy-1,2,3,4-tetrahydro-2,6,11-naphthacenetrione. The conventional cyanohydrin formation of this sample followed by acid hydrolysis gave (±)-2,5,12-trihydroxy-6,11-dioxo-1,2,3,4-tetrahydro-2-naphthacenecarboxylic acid. The racemic acid was found to be cleanly resolved by forming a salt with (−)-N-methylephedrine, furnishing optically pure (R)-carboxylic acid. Successive treatments of the (R)-carboxylic acid with N,N′-carbonyldiimidazole and methylmagnesium bromide in the presence of trimethylsilyl triflate readily produced optically pure (R)-(−)-7-deoxy-4-demethoxydaunomycinone, the key synthetic intermediate of (+)-4-demethoxydaunomycinone.