Exploiting Chemo- and Stereoselectivity by means of medium-engineering: squeezing ADHs for divergent processes

FABRICIO R. BISOGNO; ANÍBAL CUETOS; ALEJANDRO A. ORDEN; MARCELA KURINA-SANZ; IVÁN LAVANDERA; VICENTE GOTOR

Hamburg

Congreso; BIOCAT 2010; 2010

Hamburg University of Technology

Enantiopure terminal halohydrins and epoxides are valuable functionalities in pharmaceutical industry and naturalproducts synthesis due to their high reactivity allowing the obtaining of a huge variety of compounds.[1]Thus, employing α-bromo ketones[2] instead of α-chloro ketones,[3] we could synthesise enantioenriched terminal oxiranesor bromohydrins at well tolerated pH conditions for the enzyme in one-pot by using ADHs.After a deep optimization of several parameters such as pH, organic co-solvent, temperature, etc. a simple biphasicsystem rendered the desired products with outstanding selectivities.Besides, syntheses of either 5 or 6-membered azacycles could be developed starting from the same substrate, statingfor the chemodivergency of the whole process.In conclusion, we have developed an efficient one-pot chemo- and stereodivergent enzymatic process leading to eitherenantiopure terminal epoxides or β-bromo alcohols starting from the corresponding α-bromo ketones. This is a nice exampleof medium engineering[4] enabling the selective formation of both antipodes of several derivatives in high yields.Furthermore, applying this chemodivergent methodology, very interesting compounds such as prolinol or piperidin-3-olcould readily be synthesised.