Synthesis of rigid and C2-symmetric pyridino-15-crown-5 type macrocycles bearing diamide–diester functions: enantiomeric recognition for chiral primary organoammonium perchlorate salts

Four novel C2-symmetric macrocyclic compounds with a pyridine function and possessing amide and ester lingeages were prepared. The enantiomeric discrimination abilities of these macrocycles against α-phenylethylammonium and α-(1-naphthyl)ethylammonium perchlorate salts were measured by standard 1H NMR titration techniques in DMSO-d6. A binding constant ratio of 31 (Kbind(S)/Kbind(R)) for two enantiomers of α-(1-naphthyl)ethylammonium salt with the macrocyclic host (S,S)-4 bearing phenyl arms was observed, which corresponds to an enantiomeric discrimination of approximately 94%. Molecular dynamic calculations were performed for some of the supramolecular complexes to in order to gain insight into the mode of molecular recognition between the macrocyclic compounds and ammonium salts; these results were consistent with experimental observations, which may be relevant to those in biochemical processes occurring in organisms.

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N,N′-Bis(1S)-1-phenyl-2-hydroxyethyl]ethanediamide[α]D25=-35.2 (c 1, DMSO)Source of Chirality: l-phenylglycinolAbsolute configuration: (S,S)

N,N′-Bis(1S)-1-benzyl-2-hydroxyethyl]ethanediamide (S,S)-2b[α]D25=-43.8 (c 0.03, MeOH)Source of Chirality: l-phenylalanineAbsolute configuration: (S,S)

N,N′-Bis(1S)-2-hydroxyethyl-1-isobutyl]ethanediamide[α]D25=-30.5 (c 1, DMSO)Source of Chirality: l-leucineAbsolute configuration: (S,S)

N,N′-Bis(1R)-1-ethyl-2-hydroxyethyl]ethanediamide[α]D25=+30.3 (c 1, DMSO)Source of Chirality: (R)-(−)-2-amino-1-butanolAbsolute configuration: (R,R)

(5S,10S)-5,10-Diphenyl-3,12-dioxa-6,9,18-triazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,7,8,13-tetraone[α]D34=-58 (c 0.04, CH3CN)Source of Chirality: l-phenylglycinolAbsolute configuration: (S,S)

(5S,10S)-5,10-Bis(2-methylpropyl)-3,12-dioxa-6,9,18-triazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,7,8,13-tetraone[α]D33=-62.0 (c 0.1, CH3CN)Source of Chirality: l-phenylalanineAbsolute configuration: (S,S)

(5S,10S)-5,10-Dibenzyl-3,12-dioxa-6,9,18-triazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,7,8,13-tetraone[α]D34=+153.0 (c 0.03, CH3CN)Source of Chirality: l-leucinolAbsolute configuration: (S,S)

(5R,10R)-5,10-Diethyl-3,12-dioxa-6,9,18-triazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,7,8,13-tetraone[α]D34=+96 (c 0.2, CH3CN)Source of Chirality: (R)-(−)-2-amino-1-butanolAbsolute configuration: (R,R)