By Nelson Bonilla

Faculty Mentor: Dr. Davis Oldham

Abstract

Asymmetric Synthesis of the Stereoisomers of Myclobutanil and its Metabolites

Nelson Bonilla and E. Davis Oldham

Myclobutanil (MT) is a chiral triazole fungicide whose main use in agriculture is the inhibition of vital fungal enzymes, thereby inhibiting fungal growth in crops. MT has exhibited low levels of toxicity but has been observed to lead to reproductive inhibition and liver toxicity in vivo. MT is metabolized enantioselectively in rats into 5 chiral metabolites. The impact of MT metabolites’ stereochemistry on their toxicity has not been well explored, nor have the enantiomers of MT been synthesized. To synthesize MT, 4-chlorobenzyl cyanide was alkylated using 1-bromobutane. Subsequent addition of formaldehyde to produce 2-(4-chlorophenyl)-2-hydroxymethylbutanenitrile. Followed by a mesyl chloride alcohol activation reaction to yield 2-(4-chlorophenyl)-2-methylsulfonatebutanenitrile. Subsequent substitution of methyl sulfonate with 1,2,4-1H-triazole produced MT. To synthesize oxidative MT Metabolites, future studies will use alkenyl halides instead of 1-bromobutane to yield MT derivatives that will be oxidized to produce the target oxidative Metabolites.