Selectivity of biohydroxylation with Beauveria bassiana of trans-2-fluorocycloalkyl N-phenylcarbamates.
Biohydroxylation with Beauveria bassiana of racemates and the pure enantiomers of trans-2-fluorocyclohexyl- 3 and trans-2-fluorocycloheptyl N-phenylcarbamates 6 were investigated and compared with results found for the corresponding nonfluorinated parent compounds. In all cases, mixtures of diastereomeric products hydroxylated in the 4-position were isolated, besides products of p-hydroxylation of the aromatic ring and succeeding compounds derived from these primary reaction products. The regioselectivity of hydroxylation by this fungus is not changed by a single fluorine substituent attached closely to the electron-rich anchoring group in the trans-2-position. There is a different influence on the diastereoselectivity of hydroxylation depending on the absolute configuration of the fluorinated substrates. While the transformation of the (S,S)-2-fluorocycloalkyl N-phenylcarbamates is not diastereoselective giving almost 1:1 mixtures of cis- and trans-4-hydroxyl compounds, the corresponding reactions of the (R,R)-isomers led preferentially to the products trans-hydroxylated in the 4-position. The transformation of the racemic fluorinated six-membered N-phenylcarbamate 3 led to products having a very small enantiomeric excess. The fluorine substituent slightly increased the enantioselectivity of transformation of the racemic seven-membered substrate 6 compared to the C(s)()-symmetric nonfluorinated carbamate. Thus, the fluorine substituent in the trans-2-position in these examples did not change the regioselectivity but rather influenced the stereochemistry of biotransformation, depending on the absolute configuration of the substrate and ring size.
Haufe
Günter
G
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, D-48149 Münster, Germany. haufe@uni-muenster.de
Wölker
Dörthe
D
Fröhlich
Roland
R
D001711:Biotransformation; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D005658:Fungi / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000378:metabolism*; D006900:Hydroxylation; D008049:Lipase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011549:Pseudomonas / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002219:Carbamates; D006845:Hydrocarbons, Fluorinated; D008049:Lipase