Loandos María del H, Villecco Margarita B, Burgueño-Tapia Eleuterio, Joseph-Nathan Pedro, Catalán César A N
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.
Nat Prod Commun. 2009 Nov;4(11):1537-45.
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.
首次制备了对映体纯的(1S,4S)-(-)-3-氧代-1,8-桉叶素(-)-2和(1R,4R)-(+)-3-氧代-1,8-桉叶素(+)-2，并通过振动圆二色性(VCD)测量确定了它们的绝对构型。因此，用乙酸铬酰处理桉叶素1得到外消旋体2，经硼氢化钠还原和乙酰化后得到外消旋的3-内乙酰氧基-1,8-桉叶素，即外消旋体4。使用猪肝酯酶(PLE)进行对映选择性水解得到3-内羟基-1,8-桉叶素(-)-3和3-内乙酰氧基-1,8-桉叶素(+)-4的混合物。经色谱分离后，(-)-3被氧化为(+)-2，而(+)-4被水解为(+)-3，然后被氧化为(-)-2。通过VCD光谱结合理论水平为B3LYP/DGDZVP的密度泛函理论(DFT)计算确定了两种酮2的绝对构型，由此可知(+)-2对映体对应于(1R,4R)-1,3,3-三甲基-5-氧代-2-氧杂双环[2.2.2]辛烷，(-)-2对映体对应于(1S,4S)分子，这也与通过莫舍尔方法推导的起始手性醇的绝对构型一致。澄清了一些文献中的不一致之处。此外，还通过使用PLE的对映选择性不对称化从内消旋二乙酸酯5制备了对映体纯的单酯(1S,3S,4R,5R)-(-)-3-乙酰氧基-5-羟基-1,8-桉叶素6和酮酯(1R,3S,4R)-(+)-3-乙酰氧基-5-氧代-1,8-桉叶素7。
