The Asymmetric Reduction Of Acenaphthenequinone And Substituted Acenaphthenequinones By Biocatalysts

Recently, biocatalysis have provided numerous chiral compounds for greatly promoting the development in the medicine, pesticide, food and functional materials field. Therefore, the biocatalysis has become a very important research area.It is well documented that most biocatalysts have the ability to reduce the aliphatic ketone and simple aromatic ketone. However, biocatalyst-mediated asymmetric reduction of polycyclic aromatic ketone was rarely. On the other hand, chiral polycyclic aromatic alcohols with rigid structures are widely used as synthetic building blocks for pharmaceuticals intermediates, transition metal ligands, analytical reagents and functional materials. Therefore, in this dissertation, we applied baker’s yeast, plant cell and Aspergillus flavus as biocatalyst to mediate the asymmetric reduction of acenaphthenequinone and substituted acenaphthene-qumones.Firstly, the reasibility of asymmetric reduction of acenaphthenequinone was study using baker’s yeast as biocatalyst. In view of the poor solubility of acenaphthenequinone, the effects of the mixing method and organic cosolvent on the reduction were examined. On this basis, the other biocatalysts such as plant cells and aspergillus flavus were also applied to study the asymmetric reduction of acenaphthenequinone. The results showed that:1. Baker’s yeast mediated-reduction of the aryl a-diketone gave mono-alcohol and di-alcohol in initial reaction time. The substrate was consumed in the initial4h of reaction time, at the same time, content of mono-alcohol,2-hydroxyacenaphthenone increase in the initial time then decrease. While the content of di-alcohol,1,2-dihydroxyacenaphthene is increasing with the time. When the reaction was performed after12h the trend of increase has a significant improment, and when the reduction proceeded for48h, the content of1,2-dihydroxyacenaphthene reached98%.2. Various plants cell were proven to reduce acenaphthenequinone to afford mono-hydroxyl ketone, exclusively. This results indicated that the plants cell show a different catalytic perfomance with baker’s yeast in activity and enantioselectivity. Among the screened six plants cell, the carrot (Daucus carota L.) and Peach (Prunus persica (L.) Batsch.) exhibited high efficiency in preparing hydroxyacenaphthenone, and up to81%ee of (-)-mono-hydroxyl ketone and86%ee of (+)-mono-hydroxyl ketone were obtained.3. Aspergillus Niger can also catalyze the asymmetric reduction of acenaphthenequinone. The reaction process is similar to that of baker’s yeast, however, a lower catalytic activity was observed.Furthermore, to expand the substrate scope of baker’s yeast-catalyzed reduction and obtain more valuable chiral aromatic alcohol, eight5-substituted acenaphthenequinones (5-bromo,5-nitro,5-methoxy,5-azido,5-amino,5-acetamido,5-chloro and5-iodo) were synthesized with acenaphthenenquinone as raw material by reaction of bromination, nitration, substitution, thermal decomposition and diazotization. Using5-bromoacenaphthenequinone and5-methoxyacenaphthenequinone as the substrates, the catalytic performance of baker’s yeast-mediated asymmetric reduction of polycyclic aromatic ketone was studied. The results show that only2-hydroxy-6-methoxyacenaphthenenone (55%ee) was produced exclusively when5-methoxyacenaphthenequinone as the substrate, which indicated that baker’s yeast-mediated reduction of polycyclic aromatic keto shows a good regioselectivity. In the presence of dimethyl sulfoxide (DMSO) as cosolvent and under vigorous agitation, both more than99%ee of cis-and trans-5-methoxy-1,2-dihydroxyacenaphthene were obtained.Finally, we have performed a study for reductive metabolism of nitroaromatic compounds by several liver microsomes from mammalian, pisces and aves, and found that all of the organisms exhibit the same metabolism process. Among the tested animal’s liver microsomes, the pig’s liver microsome exhibited the highest reactivity and chemoselectivity. Using4-nitrophthalonitrile (Xa) as substrate, the selectivity was reached the highest and hydroxylamine/amine=71/29when the reaction proceeded for1h. When the reaction proceeded for8h, the hydroxylamine was transformed to corresponding amine compound completely, and the conversion can reached48%. Further prolonging the reaction time up to48h, more than97%of1a was converted. Under the optimized conditions, pig’s liver microsome was applied to reduce other nitroaromatic compounds (Ⅺa-ⅩⅥa). There are some differences in the conversion and selectivity along with various substrates. Among them, compound Ⅷa exhibits the lowest reactivity and only5%was converted when the reaction was performed for4h, meanwhile selectivity for hydroxylamine/amine reached54/46. By contrast, compound XVa shows the highest reactivity up to98%conversion, however the selectivity for hydroxylamine reached95%at the same reaction conditions.