Lipase-mediated resolution of 3-hydroxy-4-trityloxybutanenitrile: synthesis of 2-amino alcohols, oxazolidinones and GABOB

Lipase-mediated kinetic resolution of 3-hydroxy-4-trityloxybutanenitrile gave the (S)-alcohol and (R)-acetate in good yields and high enantioselectivities. The resolution using Pseudomonas cepacia lipase (Burkholderia cepacia) immobilized on modified ceramic particles (PS-C) in diisopropyl ether gave the best results. The use of base additives in this transesterification drastically reduces the reaction time without effecting the yields or enantioselectivities. Resolved 3-hydroxy-4-trityloxybutanenitrile has been utilized for the synthesis of enantiomerically pure 5-tosyloxymethyl-1,3-oxazolidine-2-one, which is an important intermediate for the preparation of β-adrenergic blocking agents and oxazolidinone based antimicrobial agents. Enantiomerically pure (R)-3-hydroxy-4-trityloxybutanenitrile and (S)-5-tosyloxymethyl-1,3-oxazolidine-2-one have been utilized in the enantioconvergent synthesis of (R)-GABOB.

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(R)-3-Hydroxy-4-tosyloxybutanenitrileC11H13NO4S[α]D26=+13.5 (c 1.45, EtOH)Source of chirality: enzymatic resolutionAbsolute configuration: R

(S)-3-Hydroxy-4-triphenylmethoxybutanenitrileC23H21NO2Ee = >99%[α]D29=-7.6 (c 1.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: S

(R)-3-Acetyloxy-4-triphenylmethoxybutanenitrileC25H23O3NEe = >99%[α]D29=+24.4 (c 1.35, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: R

(S)-3-Hydroxy-4-triphenylmethoxy butanamideC23H23O3N[α]D27=-18.1 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: S

(S)-5-Trityloxymethyl-2-oxazolidinoneC23H21O3[α]D26=+25.0 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: S

(S)-5-Tosyloxymethyl-1,3-oxazolidine-2-oneC11H13NO5S[α]D27=+45.4 (c 1.25, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: S

(R)-5-Hydroxymethyl-1,3-oxazolidine-2-oneC4H7NO3[α]D27=-33.3 (c 0.45, EtOH)Source of chirality: enzymatic resolutionAbsolute configuration: R

(R)-5-Azidomethyl-1,3-oxazolidine-2-oneC4H6N4O2[α]D29=-62.2 (c 1.12, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: R

(R)-5-Cyanomethyl-1,3-oxazolidine-2-oneC5H6N2O2[α]D26=+4.5 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: R

(R)-GABOBC4H9NO3[α]D28=-20.7 (c 1.0, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: R