Synthesis of novel C2-symmetric chiral crown ethers and investigation of their enantiomeric recognition properties

A series of new C2-symmetric chiral aza crown ether macrocycles 1–4 have been synthesized from (S)-3-aryloxy-1,2-propanediol and (S)-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives. These new macrocycles have been shown to be strong complexing agents for primary organic ammonium salts (with K up to 176.93 M−1 and ΔG° up to 12.81 kJ mol−1) by 1H NMR titration. These macrocyclic host exhibited enantioselective bonding toward the d-enantiomer of phenylalanine methyl ester hydrochloride with KD/KL up to 6.87 in CDCl3 with 0.25% CD3OD.

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(2S,9S)-4,7-[N-(S)-α-Phenyl ethyl]diaza-2,9-decanediolC24H36O2N2[α]D25=-72.9 (c 3.4, CHCl3)Source of chirality: (S)-2-propanediolAbsolute configuration: (2S,9S)

(1S,8S)-3,6-[N-(S)-α-Phenyl ethyl]diaza-1,8-diphenoxymethyl-1,8-decanediolC36H44O4N2[α]D34=-40.5 (c 0.74, CHCl3)Source of chirality: (S)-3-phenoxypropane-1,2-diolAbsolute configuration: (1S,8S)

(6S,17S)-1,4-[N-(S)-α-Phenylethyl]-diaza-6,17-dimethyl-7,10,13,19-tetraoxacyclooctadecaneC30H46N2O4[α]D30=+41 (c 2.5, CHCl3)Source of chirality: (S)-1,2-propanediolAbsolute configuration: (6S,17S)

(6S,17S)-1,4-[N-(S)-α-Phenylethyl]-diaza-6,17-dimethyl-11,12-benzo-7,10,13,19-tetraoxacyclooctadec-11-eneC34H46N2O4[α]D30=+85 (c 2.5, CHCl3)Source of chirality: (S)-1,2-propanediolAbsolute configuration: (6S,17S)

(6S,17S)-1,4-[N-(S)-α-Phenylethyl]-diaza-6,17-diphenoxymethyl-7,10,13,19-tetraoxacyclooctadecaneC42H54N2O6[α]D32=+87 (c 1, CHCl3)Source of chirality: (S)-3-phenoxypropane-1,2-diolAbsolute configuration: (6S,17S)

(6S,17S)-1,4-[N-(S)-α-Phenylethyl]-diaza-6,17-diphenoxymethyl-11,12-benzo-7,10,13,19-tetraoxacyclooctadec-11-eneC46H54N2O6[α]D30=+89 (c 2.5, CHCl3)Source of chirality: (S)-3-phenoxypropane-1,2-diolAbsolute configuration: (6S,17S)