Bioconversion of indene to trans-2S,1S-bromoindanol and 1S,2R-indene oxide by a bromoperoxidase/dehydrogenase preparation from Curvularia protuberata MF5400

New frontiers in biological halogenation

“…The use of haloperoxidases as halogenating biocatalysts is limited because haloperoxidase‐catalysed halogenations lack substrate specificity and regioselectivity, which is consistent with the premise that hypohalous acid is the actual halogenating reagent. Nevertheless, the halogenating activity of haloperoxidases may have some biocatalytic potential; the biotransformation of indene to 1 S ,2 R ‐indene oxide, which is required in the synthesis of the HIV‐1 protease inhibitor Crixivan® (Merck), can be catalysed by a crude enzyme extract of the fungus Curvularia protuberata (Zhang et al. 1999).…”

“…The use of haloperoxidases as halogenating biocatalysts is limited because haloperoxidase-catalysed halogenations lack substrate specificity and regioselectivity, which is consistent with the premise that hypohalous acid is the actual halogenating reagent. Nevertheless, the halogenating activity of haloperoxidases may have some biocatalytic potential; the biotransformation of indene to 1S,2R-indene oxide, which is required in the synthesis of the HIV-1 protease inhibitor CrixivanÒ (Merck), can be catalysed by a crude enzyme extract of the fungus Curvularia protuberata (Zhang et al 1999). It was found that the extract contained a bromoperoxidase, which converted indene to racemic trans-bromoindanols, and a dehydrogenase that stereoselectively oxidized the 2R,1R-bromoindanol to bromoindenol, leaving the 2S,1S-bromoindanol which yielded the epoxide upon the addition of base ( Fig.…”

Haloperoxidase Enzymes as ‘Redox Catalysts’ Important for Industrial Biocatalysis

“…Some of these sulfoxidation reactions can be stereospecific (Coughlin et al 1993). The biotransformation of indene to 1S,2R-indene oxide with an extract of a Curvularia fungus is used, for instance in the synthesis of the HIV protease inhibitor Crixivan ® (Merck) (Zhang et al 1999) (Fig. 9).…”

Synthesis of enantiomerically pure trans‐(1R,2R)‐ and cis‐(1S,2R)‐1‐amino‐2‐indanol by lipase and ω‐transaminase

“…Biocatalytic methods have been adopted as efficient procedures for the asymmetric preparation of cis-AI. Merck group used Culvularia protuberata MF 5400 to convert indene to chiral (1S,2S)-bromoindanol, which was subsequently converted to the desired cis-AI (Zhang et al, 1999). Enantiomerically pure cis-and trans-AI can also be prepared using lipase-catalyzed enantioselective transesterification of racemic cis-2-azido-1-indanol or trans-2-bromo-1-indanol (Mitrohikine et al, 1995a,b).…”