Preparation Of Chiral Aceanthylrene-1,2-diols By Baker’s Yeast And Its Application

The optical active alcohol as "chiral building blocks" is important in the synthesis of natural products and chiral drug. Compared with binaphthalenes, chiral aceanthrene-1,2-diols have a better rigid structure, which may have a potential value in chiral recognition or as chiral ligands. Owing to the structural and electronic symmetry of the two carbonyls, it was hard to achieve the high optical active aceanthylrene-1,2-diols from the traditional chemical synthesis methods, and there was no relative report by far.In this paper, we explored and achieved the high optical activity aceanthylrene-l,2-diols (trans-3) using baker’s yeast as biocatalyst, and a series of explorations were carried out to find out the suitable agitator, co-solvent and feed methods. The enantiomeric excess and the conversion were tracked by HPLC with a chiral AD-H column. The study showed that under vigorous stirring (>600rpm/min) and in the presence of DMSO as co-solvent, we could obtained trans-3with98%e.e. by baker’s yeast catalyzed reduction, meanwhile it was found that trans-3could reach15%yield by feeding reagent as a batch. The absolute configuration was confirmed as (S, S) by circular dichroism methods.Use trans-3as chiral pool, we had designed a chiral probe based on the PET mechanism for recognizing sugar compound, Unfortunately we didn’t get it for the difficulties of the synthesis, The synthesis method needed to be further optimized.As the unprecedented application of enzyme-catalyzed reactions in the field of organic synthesis, our research group have reported reduction of substituted fluorenones and substituted acenaphthenequinones by baker’s yeast with high enantioselectivity. These results indicate that even with highly sterically hindered aromatic ketones also can be reduced in the enzyme medium, as long as the mass-transfer limitation in the medium is overcome. As part of our continued interest in enzyme chemistry, we herein to report the third example of using enzyme systems as reducing agent for the enantioselective reduction of polycyclic aromatic ketones.