Stereoselective epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile

Bioorg Med Chem. 1994 Jun;2(6):535-42. doi: 10.1016/0968-0896(94)80024-3.

Abstract

The chiral intermediate (3S,4R)-trans-3,4-dihydro-3,4-dihydroxy-2,2-dimethyl- 2H-1-benzopyran-6-carbonitrile [(+)-trans diol 3] was made by the stereoselective microbial epoxidation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 1. This compound is a potential intermediate for the total synthesis of potassium-channel openers. Several microbial cultures were found which catalyzed the transformation of 1 to the corresponding (3S,4S)-epoxide 2 and (+)-trans diol 3. The two best cultures, Corynebacterium sp. SC 13876 and Mortierella ramanniana SC 13840 gave reaction yields of 32 M% and 67.5 M% and optical purities of 88 and 96%, respectively, for (+)-trans diol 3. A single-stage process (fermentation-epoxidation) for the biotransformation of 1 was developed using Corynebacterium sp. SC 13876 and M. ramanniana SC 13840. In a 25-L fermentor, the (+)-trans diol 3 was obtained in 38.6 M% yield with an optical purity of 90% using Corynebacterium SC 13876. The reaction yield of 60.7 M% and optical purity of 92.5% were obtained for (+)-trans diol 3 using M. ramanniana SC 13840. A two-stage process for the preparation of (+)-trans diol 3 was also developed using a 3 L cell-suspension (10% w/v, wet cells) of M. ramanniana SC 13840. The reaction was carried out in a 5-L Bioflo fermentor. The concentration of substrate 1 was 2 g L-1 with glucose present at 10 g L-1. After 48 h, (+)-trans diol 3 was obtained in 76 M% yield with an optical purity of 96%.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Bacteria / growth & development
  • Bacteria / metabolism*
  • Benzopyrans / chemistry*
  • Corynebacterium / metabolism
  • Epoxy Compounds*
  • Fermentation
  • Fungi / growth & development
  • Fungi / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mucorales / metabolism
  • Nitriles / chemistry*
  • Nocardia / metabolism
  • Pichia / metabolism
  • Pseudomonas / metabolism
  • Rhodococcus / metabolism
  • Stereoisomerism

Substances

  • 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile
  • Benzopyrans
  • Epoxy Compounds
  • Nitriles