Transformation of (+)-thiomicamine into the p-methylthio analogue of (+)-5-epi-cytoxazone

(2S,3S)-(+)-Thiomicamine 3, a commercially available aminodiol, was transformed into (4R,5S)-5-hydroxymethyl-4-(p-methylthiophenyl)-2-oxazolidinone 10, a compound related to cytoxazone-type biologically active natural products. The synthetic strategy of the highly regio- and stereoselective synthesis was based upon the reversal of the position of the hydroxyl and amine functionalities in 3, accomplished via azidolysis of the key intermediate, epoxide 6.

Figure optionsDownload as PowerPoint slide

(1S,2S)-2-Dimethylamino-1-(4-methylthiophenyl)-1,3-propanediolC12H19NO2S[α]D = +35.6 (c 1.0, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (1S,2S)

(1S,2S)-2-Dimethylamino-1-(4-methylthiophenyl)-1,3-propanediol methiodideC13H22NO2SI[α]D = +46.1 (c 0.98, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (1S,2S)

(2R,3S)-2,3-Epoxy-3-(4-methylthiophenyl)-1-propanolC10H12O2S[α]D = +41.6 (c 0.97, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (2R,3S)

(2S,3R)-3-Azido-3-(4-methylthiophenyl)-1,2-propanediolC10H13N3O2S[α]D = −200.2 (c 0.98, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (2S,3R)

(2S,3R)-3-Azido-1,2-diphenyloxycarbonyloxy-3-(4-methylthiophenyl)-propaneC24H21N3O6S[α]D = −44.7 (c 0.86, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (2S,3R)

(4R,5S)-4-(4-Methylthiophenyl)-5-phenyloxycarbonyloxy-2-oxazolidinoneC18H17NO5S[α]D = +72.2 (c 0.64, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (4R,5S)

(4R,5S)-5-Hydroxymethyl-4-(4-methylthiophenyl)-2-oxazolidinoneC11H13NO3S[α]D = +31.9(c 0.9, MeOH)Source of chirality: (+)-thiomicamineAbsolute configuration: (4R,5S)