Enzymatic resolution of 5-hydroxy- and 8-hydroxy-2-tetralols using immobilized lipases

(R)-2-Tetralol (R)-2a, (R)-5-hydroxy-2-tetralol (R)-2b and (R)-8-hydroxy-2-tetralol (R)-2c, which are key intermediates in the synthesis of pharmacologically active 2-aminotetralins 3, were prepared in moderate to very high enantiomeric excess (up to 99% ee) by enzymatic resolution of the corresponding racemic butyrates rac-1a, rac-1b and rac-1c, respectively, using lipases immobilized on octyl agarose. This methodology is an alternative to the microbial reduction of 2-tetralones.

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(R)-8-Hydroxy-2-tetralolC10H12O2Ee = 99%[α]D25=+92.5 (c 0.5, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(S)-8-Hydroxy-2-tetralyl butyrateC14H18O3Ee = 99%[α]D25=-39.2 (c 0.5, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

(R)-5-Hydroxy-2-tetralolC10H12O2Ee = 71%[α]D25=+50.6 (c 0.5, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(S)-5-Hydroxy-2-tetralyl butyrateC14H18O3Ee = 65%[α]D25=-21.5 (c 0.5, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (S)