Synthesis of planar chiral [2.2]paracyclophanes by biotransformations: kinetic resolution of 4-formyl-[2.2]paracyclophane by asymmetric reduction

✍ Scribed by Dirk Pamperin; Henning Hopf; Christoph Syldatk; Markus Pietzsch

• Book ID: 104360959
• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 411 KB
• Volume: 8
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/s0957-4166(96)00503-4

✦ Synopsis

The synthesis of enantiomerically pure (S)-4-formyl-[2.2]paracyclophane 1 (>99% ee) and (R)-4-hydroxymethyl-[2.2]paracyclophane 2 (>78% ee) was achieved by bioreduction of (RS)-I with a yield of 49 and 34% respectively. From several microorganisms screened only a strain of the yeast Saccharomyces cerevisiae (DSM 11285) showed a stereospecific reduction of this planar chiral substrate (E>100). Despite the high enantiomeric ratio, it is necessary to maintain the conversion at almost 50% in order to obtain a high enantiomeric excess of both substrate and product of the reduction reaction. Tween 80 together with methanol was found to be the most suitable cosolvent mixture which enhances the solubility of the substrate and does not effect the biocatalyst. For the calculation of E the enantiomeric excesses of substrate and product were measured at various conversions by chiral gas chromatography. Commercially available alcohol dehydrogenases such as HLADH, YADH and TBADH were tested for the desired reaction too, but found to be completely inactive.