Stereoselective microbial/enzymatic oxidation of (exo, exo)-7-oxabicyclo [2.2.1] heptane-2,3-dimethanol to the corresponding chiral lactol and lactone

A key chiral intermediate, lactol 2[3aS(3aα, 4α, 7α, 7aα)]-hexahydro-4,7-epoxy-isobenzofuran-1 (3H)-one, and the corresponding chiral lactone 3 were made in high optical purity by stereoselective enzymatic and microbial oxidation of the parent diol 1 . Horse liver alcohol dehydrogenase (HLADH) in the presence of nicotinamide adenine dinucleotide (NAD + ) and riboflavin oxidized diol 1 (exo, exo)-7-oxabicyclo [2.2.1] heptane-2,3-dimethanol to the corresponding lactol 2 and lactone 3 . Regeneration of NAD + required for the oxidation of diol 1 was carried out by the NADH-dependent alanine dehydrogenase and leucine dehydrogenase in the presence of alanine and leucine, respectively. Since expensive enzyme (HLADH) and cofactors (NAD + ) were required for the oxidation reaction, various microorganisms were screened for the ability to catalyze the stereoselective oxidation of diol 1 . Two organisms, Nocardia globerula ATCC 21505 and Rhodococcus sp. ATCC 15592, catalyzed the efficient oxidation of diol 1 to the corresponding chiral lactol 2 and lactone 3 . The reaction yield of 70% and optical purity of 96% was obtained for lactone 3 prepared from the oxidation of diol 1 by cell suspensions (10% w/v, wet cells) of N. globerula ATCC 21505. Substrate was used at 5 gl −1 concentration. A 10% (w/v, wet cells) cell suspension of Rhodococcus sp. ATCC 15592, after 120 h reaction period, produced lactol 2 in 12% yield and lactone 3 in 34% yield. An overall 46% reaction yield was obtained based on diol 1 oxidation. Substrate was used at 5 gl −1 concentration. Optical purity of 96.7% and 98.4% was obtained for lactol 2 and lactone 3 , respectively. Lactone 3 purified by slilica gel chromatography gave a specific rotation of +117° and enantiomeric excess of >99%.