Application of cyclic sulfates in the synthesis of enantiomers of 1-[3-(4-aryl-piperazin-1-yl)-2-hydroxy-propyl]-pyrrolidin-2-one

The synthesis of enantiomers of 1-[3-(4-aryl-piperazin-1-yl)-2-hydroxy-propyl]-pyrrolidin-2-one derivatives is described. These enantiomers were synthesized starting from (R)- or (S)-1-chloro-2,3-dihydroxypropane using relevant cyclic sulfates as chiral intermediates. The enantiomeric purities of the final compounds were in the range of 99.3–100.0%, as determined by high performance liquid chromatography. The final compounds were found to display moderate potency as ligands for α1-adrenoreceptors.

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(R)-4-Chloromethyl-[1,3,2]dioxathiolane-2-oxideC3H5O3SCl[α]D20=-44.65 (c 1, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (R)

(R)-4-Chloromethyl-[1,3,2]dioxathiolane 2,2-dioxideC3H5O4SCl[α]D20=+4.2 (c 1, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (R)

(S)-1-(3-Chloro-2-hydroxy-propyl)-pyrrolidin-2-oneC7H12O2NCl[α]D20=+30.9 (c 1, MeOH)Source of chirality: chiral substrateAbsolute configuration: (S)

(R)-1-[2-Hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-pyrrolidin-2-oneC17H25N3O2[α]D20=+10.3 (c 1, EtOH)Source of chirality: chiral substrateAbsolute configuration: (R)

(R)-1-[2-Hydroxy-3-[4-(2-chlorophenyl)piperazin-1-yl]-propyl]-pyrrolidin-2-oneC17H24N3O2Cl[α]D20=+19.9 (c 1, EtOH)Source of chirality: chiral substrateAbsolute configuration: (R)

(S)-1-[2-Hydroxy-3-[4-(2-ethoxyphenyl)piperazin-1-yl]-propyl]-pyrrolidin-2-oneC19H29N3O3[α]D20=-18.4 (c 1, EtOH)Source of chirality: chiral substrateAbsolute configuration: (S)