STEREOSPECIFIC BIOHYDROXYLATIONS OF PROTECTED CARBOXYLIC-ACIDS WITH CUNNINGHAMELLA-BLAKESLEEANA

Cunninghamella blakesleeana DSM 1906 was found to be an efficient bioc atalyst for the biotransformation of cycloalkylcarboxylic acids into h ydroxy and oxo derivatives. When cultivated in submerged culture, the fungus grew in pellets. In comparison with malt extract-glucose-pepton e-yeast extract medium (medium E), Czapek-Dox medium nas found to redu ce pellet size. Cycloalkylcarboxylic acids were protected against micr obial degradation by chemical transformation into 2-cycloalkyl-1,3-ben zoxazoles. The transformations of protected cyclopentyl-, cyclohexyl-, cycloheptyl-, and cyclooctylcarboxylic acids by C. blakesleeana were investigated. The biotransformations were performed in medium E by usi ng an aerated, stirred-tank bioreactor. The transformation of 2-cyclop entyl-1,3-benzoxazole yielded (1S,3S)-3-(benz-1,3-oxazol-2-yl)cyclopen tan-1-ol as the main product. The main by-product was (1R)-3-(benz-1,3 -oxazol-2-yl) cyclopentan-1-one, and 2-(benz-1,3-oxazol-2-yl)cyclopent an-1-ol was also obtained in small amounts. During the experiment, the enantiomeric excess of the main product increased up to 64%. 2-Cycloh exyl-1,3-benzoxazole was hydroxylated to 4-(benz-1,3-oxazol-2-yl)cyclo hexan-1-ol. 2-Cycloheptyl-1,3-benzoxazole and 2-cyclooctyl-1,3-benzoxa zole were transformed into several alcohols and ketones, all in low yi elds (2 to 19%).