Preparation and absolute configuration of (1R,4R)-(+)-3-oxo-, (1S,4S)-(-)-3-oxo- and (1R,3S,4R)-(+)-3-acetyloxy-5-oxo-1 ,8-cineole.
Enantiomerically pure (1S,4S)-(-)-3-oxo-1,8-cineole (-)-2 and (1R,4R)-(+)-3-oxo-1,8-cineole (+)-2 were prepared for the first time and their absolute configurations assigned by vibrational circular dichroism (VCD) measurements. Thus, treatment of cineole 1 with chromyl acetate gave rac-2 which after sodium borohydride reduction and acetylation provided racemic 3-endo-acetyloxy-1,8-cineole, rac-4. Enantioselective hydrolysis using porcine liver esterase (PLE) gave a mixture of 3-endo-hydroxy-1,8-cineole (-)-3 and 3-endo-acetyloxy-1,8-cineole (+)-4. After chromatographic separation, (-)-3 was oxidized to (+)-2, while (+)-4 was hydrolysed to (+)-3 and then oxidized to (-)-2. The absolute configuration of either ketone 2 was established by VCD spectroscopy in combination with density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory, from where it followed that the (+)-2 enantiomer corresponds to (1R,4R)-1,3,3-trimethyl-5-oxo-2-oxabicyclo[2.2.2]octane and the (-)-2 enantiomer to the (1S,4S) molecule which is also in agreement with the absolute configuration deduced by the Mosher method for the starting chiral alcohols. Some literature inconsistencies are clarified. In addition, the enantiomerically pure monoester (1S,3S,4R,5R)-(-)-3-acetyloxy-5-hydroxy-1,8-cineole 6 and the ketoester (1R,3S,4R)-(+)-3-acetyloxy-5-oxo-1,8-cineole 7 were prepared from meso-diacetate 5 by enantioselective asymmetrization also using PLE.
Loandos
María del H
Mdel H
lNQUINOA-CONICET and Instituto de Química Orgánica, Facultad de Bioquimica Quimica y Farmacia, Universidad Nacional de Tucuman, Ayacucho 471, S. M de Tucumin, T4000INI, Argentina.
Villecco
Margarita B
MB
Burgueño-Tapia
Eleuterio
E
Joseph-Nathan
Pedro
P
Catalán
César A N
CA
D002942:Circular Dichroism; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D039821:Monoterpenes / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
C546649:3-acetyloxy-5-oxo-1 ,8-cineole; D007202:Indicators and Reagents; D039821:Monoterpenes