Enzymatic resolution of racemates is a popular industrial process which is often coupled with racemisation of the unwanted isomer in a method known as dynamic resolution. The benefits are:

• Greater than 50% yield of product can be achieved
• The need to remove and separately recycle the unwanted isomer is eliminated, making for a much simpler work-up
• Enantioselectivity usually remains constant as the "wrong" enantiomer is racemised.

Although the benefits of dynamic resolution are evident, in practice, there are relatively few examples with enzymes, since racemisation conditions may be incompatible with enzyme activity. Workers at DuPont Pharmaceutical (now part of Bristol Myers Squibb) have now reported a Tandem reversible Michael addition - enzymatic hydrolysis which is a new variant of dynamic resolution (Pesti J A et al, J Amer Chem Soc 2001, 11075).

The arylisoxazoline below is easily resolved and the unwanted isomer can be racemised under mild basic conditions, but conditions whereby the resolution/racemisation could be coupled could not be found. Since it was speculated that the racemisation occurs via ring opening - and corresponding thioesters were prepared and conditions for coupled resolution-racemisation were found. The choice of reaction conditions is crucial. At pH 9.25, phosphate buffer an amine - preferably trimethylamine rather than the usual trioctylamine - was essential to get reasonable racemisation rates. This methodology is useful in the synthesis of roxifiban, a drug in development for a range of cardiovascular disorders arising from undesired platelet adhesion.