Prepration Of Chrial 1, 2-Dioxyacenaphthene By Baker's Yeast And Exploration Of Its Application

Acenaphthene-1,2-diol derivatives are widely exsited in many biologically active compounds and also widely used as synthetic intermediates for functional materials. However, the applying of enantiomerically pure substituted acenaphthene-1,2-diol have been scarcely reported due to lacking of efficient preparation procedure to obtain them. Compared with binanaphthalenes, which are widely used in chiral recognition or as ligands of chiral catalyst, dihydroxyacenaphthenes have better rigid structures. So, dihydroxyacenaphthenes may have more potential value in these two aspects. Because of the structural and electronic symmetry of the two sides, it was difficult to obtain the enantiopure dioxyacenaphthenes from the usual chemical methods. Finding an efficient method to synthesize the chiral dihydroxyacenaphthene and developing its applying has still been a novel challenging.In this paper, we explored and achieved to obtain the enantiomerically pure acenaphthene-1,2-diols and 5-substitued-acenaphthene-1,2-diols using baker's yeast as reducing reagent. To optimize the reacting condition a series of reacts were carried out to find the proper mass-transfer driver and co-solvent. The anantiomeric excess was determined by HPLC with a chiral AD-H column and the absolute configuration was assignment by the exciton chirality circular dichroism method (ECCD). To some degree, we also made some exploring in applying of the acenaphthene-1,2-diols and its derivatives in physiologically active aspect.The 5-substitued-acenaphthylene-1,2-diones were prepared by nitration, substitution, diazotization and reduction using acenaphthylene-1,2-diones as the crude material. A series of highly enantioselective trans-5-subsitituded-acenaphthene-1,2-diols in 21～72% yield with 97～100% ee could be obtained by baker's yeast mediated reduction of corresponding 5-substituted-acenaphthylene-1,2-dione, in the presence of DMSO as co-solvent and under vigorous agitation. The absolute configuration of (-)-trans-5-methoxy-acenaphthene-1,2-diol, (-)-trans-5-methoxy-acenaphthene-1,2-diol, (-)-trans-5-bromo-acenaphthene-1,2-diol were assigned as (S,S), and (-)-trans-5-thiomorpholin-acenaphthene-1,2-diol was established as (R,R) by the exciton chirality circular dichroism method.In the measurement of Bcl-2 targeted antitumor drugs, we found the efficiency of the cis-5 thiomorpholin-dihydroxyacenathenes and these derivatives were nearly 10 times toward the corresponding trans-congiguration. On base of this result, the object products could be further modified.In the resesrch of chrial recognition, we found another dihydroxyacenaphthene derivatives could recognize L-glutamic acid to some extent, in spite of needing more identification.On the basis of baker's yeast-catalyzed reduction of fluorenones, the substrate of the baker's yeast reductions was extended in the research. It further proved that if the obstacle of mass-transfer was overcomed, rigid and polycyclic aromatic ketones could be reduced by baker's yeast.