R -3- 4-Fluorophenyl -2-hydroxy propionic acid

R)-3-(4-fluorophenyl)-2-hydroxy propionic acid 1 is a building block for the synthesis of Rupintrivir, a rhinovirus protease inhibitor currently in human clinical trials to treat the common cold (Fig. 1) [1, 2], Retrosynthetically, Rupintrivir was prepared from four fragments the lactam derivative Pi, the chiral 2-hydroxy acid P2 (compound 1), the valine derivative P3, and an isoxazole acid chloride P4 (Fig. 1). In this chapter the preparation of 1 using a biocatalytic reduction performed in a membrane reactor will be discussed in detail. 

An efficient and practical process has been described for the synthesis of (R)-3-(4-fluorophenyl)-2-hydroxy propionic acid at a multi-kilogram scale with good overall yields (68-72% for two steps), excellent stereoselectivity (>99.9% ee), and significant cost savings. The key to the process is the use of a continuous membrane reactor which was simple in concept, low cost in design, and provided high space-time yields. This method has a broad substrate spectrum in contrast to asymmetric chemical catalysis and a variety of chiral 2-hydroxy acids can be prepared. Moreover, by alternating d-LDH with l-LDH, both enantiomers can be synthesized. 

Enzymatic Preparation of (R)-3-(4 Fluorophenyl)-2-hydroxy propionic acid... 

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