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The stereoselective synthesis of antifungal agent threo-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol (SM-8668) is described. The key step is the selective synthesis of intermediate threo-2(2,4-difluorophenyl)-2-(1-substituted ethyl)oxirane. threo-2-(2,4-Difluorophenyl)-2-(1-methylthioethyl)oxirane was synthesized threo-selectively by the reaction of 1-(2,4-difluorophenyl)-2-methylthio-1-propanone with dimethyloxosulfonium methylide in a heterogeneous media consisting of a hydrophobic solvent and aqueous alkaline solution.

The stereoselective synthesis of antifungal agent threo-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol (SM-8668) is described. The key step is the selective synthesis of intermediate threo-2(2,4-difluorophenyl)-2-(1-substituted ethyl)oxirane. threo-2-(2,4-Difluorophenyl)-2-(1-methylthioethyl)oxirane was synthesized threo-selectively by the reaction of 1-(2,4-difluorophenyl)-2-methylthio-1-propanone with dimethyloxosulfonium methylide in a heterogeneous media consisting of a hydrophobic solvent and aqueous alkaline solution.

(±)-7-Deoxy-4-demethoxydaunomycinone(±)- 3 ) was cleanly resolved by forming a mixture of the diastereomeric acetals ((−)- 9 and (+)- 10 or (+)- 9 and (−)- 10 with the title vicinal -diol((+)- or (−)- 5 ) to give optically pure (R)(−)- 3 . The method for racemizing the undesired enantiomer((S)(+)- 3 ) was also explored. Optically pure (+)-4-demethoxydauno-mycinone ((+)- 2b ) was elaborated from (R)(-)- 3 according to the reported reaction scheme.

Reduction of the racemic α-hydroxy ketones((±)-3a,b) with fermenting baker's yeast followed by fractional recrystallization and oxidation was found to readily afford optically pure anthracyclinone intermediates((R) (−)-3a,b and their partially optically active antipodes ((S)(+)-3a,b). The useless enantiomers ((S)(+)-3a,b and diastereomeric vicinal-diols((+)- 5a,b) could be recycled to (±)-3a,b and the achiral ketones(6a,b) by racemization and oxidative cleavage, respectively.

(±)-7-Deoxy-4-demethoxydaunomycinone((±)-3) was found to be cleanly resolved by forming a mixture of the diastereomereic acetals((-)-9and(+)-10 or(+)-9 and(-)-10)with the title vicinal-diol(+)-or ( )-5), affording optically pure (R)-( )-3. The resolving agents (( + )- and ( )-5) were readily synthesized from unnatural(2S,3S)-(-)-tartaric acid((-)-6)or D-(-)-mannitol and natural (2R,3R)-(+)-tartaric acid((+)6), respectively. The undesired enantiomer ((S)-(+ )-3) obtained by the optical resolution could be racemized by heating with trifluoromethanesulfonic acid in aq acetic acid. Optically pure (R)-3 was elaborated to optically pure (+)-4-demethoxydaunomycinone ((+)-2b) and (+)-demethoxyadriamycinone ((+)-2a) by featuring highly stereoselective ( ⪢ 20:1) introduction of the OH group into the C7-position as a key step.

(±)-Clivonine and (±)-clividine, lactonic alka-loids in Amaryllidaceae plants, have been synthesised.