Enzymatic reductions chiral 3-hydroxy esters

The distribution of metabolites obtained after incubation of pineapple slices with keto acids and keto esters, potential precursors of the corresponding hydroxy compounds, is summarized in Table II. The metabolization steps comprise esterification, reduction to hydroxy compounds, formation of acetoxy esters, and cyclization to the corresponding lactones. Metabolization rate and distribution of formed products strongly depend on the structures of the precursors. The detection of these metabolites proves the enzymatic capability of pineapple tissue to catalyze these conversions, an aspect which might be interesting for future use of pineapple tissue cultures in the production of chiral compounds. 

Reduction of a-keto esters. The reduction of a-keto esters by this substance has also been studied. Reduction of two a-keto acids to a-hydroxy acids has been effected in high yield, but only in the presence of Mg or Zn (as in enzymatic reactions of DPNH). Reduction involves direct transfer of hydrogen from the model compound. By use of a chiral derivative of 1-benzyl-1,4-di-hydronicotinamide reduction of ethyl benzoylformate to ethyl (R)-(-)-man-delate has been effected with an optical purity of 19%. 

Atazanavir 21 (Figure 4.23) is an acyclic aza-peptidomimetic, a potent HIV protease inhibitor [44, 45] approved by the FDA for the treatment of acquired immunodeficiency syndrome (AIDS). An enzymatic process was developed to prepare (lS,2i )-[3-chloro-2-hydroxy-l-(phenylmethyl) propyljcarbamic acid, 1,1-dimethylethyl ester 81, a key chiral intermediate in the S5mthesis of atazanavir. The diastereoselective reduction of (lS)-[3-chloro-2-oxo-l-(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 82 was carried out using Rhodococcus erythropolis to afford 81 with a >90% yield and with a diastereomeric purity of >98% and an ee of 99.4% [111],... 

---