The Aapplication Of Epoxide Hydrolase BmEH And Synthesis Of (+)-fusarisetin Analogue

This thesis consists of two aspects. In the first section, the synthesis of a series of drug precursor epoxide was conducted and used for characterization of a library of BmER hydro lase variants. Base on this, the best variant were screened against three series of epoxide substrates and the process curve of enzyme reaction were demonstrated by the real-time monitoring ee value of both epoxide and diol. With structure analysis of Guaifenesin and its derivatives combining with epoxide 2a resolution results, a series of chiral Guaifenesin derivatives were synthesized. The second part conducted the synthesis of the desmethyl (+)-Fusarisetin A. The key intermediates polyallyl esters 2-8 and pyrrolidine-2,4-ketones 2-5 were synthesized starting with 1,6-hexanediol and Z-serine. Compound 2-8 was used as substrate to explore the conditions of the intramolecular Diels-Alder reaction to constructe trans-decalin key intermediate. After that, this key intermediate was accumulate and attempted to coupled with 2-5 to finish the synthesis of demethylation of Trichosetin. Ultimately, the synthesis of C-12 demethylation of (+)-Fusarisetin A would be achieved.