Synthesis of novel cyano-cyclitols and their stereoselective biotransformation catalyzed by Rhodococcus erythropolis A4

A variety of novel cyano-cyclitols possessing complex stereochemistry have been synthesized. These compounds were subjected to the biocatalyzed hydrolysis of their nitrile groups. The bacterial strain Rhodococcus erythropolis A4, expressing a nitrile hydratase/amidase bienzymatic system, was able to recognize (1R,2S,3S,4R)/(1S,2R,3R,4S)-1-cyano-2,3,4-trihydroxy-cyclohex-5-ene and trans-3-cyanocyclohexa-3,5-diene-1,2-diol, and catalyze their transformations into the corresponding amides and acids. The kinetic and stereochemical trends of these biotransformations, a rare example of the enantiorecognition of a rigid bulky aliphatic substrate, are discussed.

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(1R,2S,3S,4R)-1-Carboxamido-2,3,4-trihydroxy-cyclohex-5-eneC7H11NO4Ee = 91.0%[α]D = −180.3 (c 0.150, MeOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (1R,2S,3S,4R)

(1S,2R,3R,4S)-2,3,4-Trihydroxy-cyclohex-5-en-1-carboxylic acidC7H10O5Ee = 74.5%[α]D = +128.2 (c 0.265, MeOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (1S,2R,3R,4S)

(1R,2R)-trans-3-Carboxyamidocyclohexa-3,5-diene-1,2-diolC7H9NO3Ee = 27.0%[α]D = −0.8 (c 0.385, MeOH)Source of chirality: enzymatic hydrolysisAbsolute configuration: (1R,2R)