The Use of Enzymes and Microorganisms in Organic Synthesis

Faculty Investigator, Stephen K. Taylor

Many lactones are important biologically and synthetically, but there are no general methods to make such compounds. We are trying to develop general methods to synthesize this important class of compounds via enzymatic or microbial methods that will produce the optically active lactones needed in modern synthetic and pharmaceutical research.

The general approaches involve the synthesis of hydroxynitrile or hydroxyester precursors via our proven enolate/epoxide reactions (see references 1-3 in my biographical sketch) and then the hydrolysis of these products can take place to lactones. The hydroxynitrile hydrolysis method has recently been developed in our lab, and involves the use of Rhodococcus rhodochrous to hydrolyze the nitrile group. The resulting hydroxyacid product then spontaneously lactonizes (equation 1).

The process takes place in minutes at pH 6 and 30 ?C. Chemical hydrolysis requires hours at elevated temperatures under highly acidic or basic conditions. Our work has been demonstrated for several different hydroxynitriles and hydroxyamide hydrolysis and is now being used to prepare pheromones. (equation 2)

As is typical of Hope College, undergraduates will have an integral part in all areas of the research. They will be closely instructed by the faculty member. They will learn the modern methods on the use of enzymes and microorganisms in organic synthesis. They will do chiral HPLC and GC work to determine enantiomeric ratios. Conventional GC and HPLC will also be used as well as 400 MHz NMR, FT-IR and other typical research tools. Many synthetic and analytical techniques will be demonstrated in the process of the research.