Lipase catalysed kinetic resolutions of 3-aryl alkanoic acids

The Use of Co-crystals for the Determination of Absolute Stereochemistry: An Alternative to Salt Formation

“…This enabled the use of chiral HPLC to directly monitor the direction of enantioselection in the enzyme mediated resolutions, Figure 5. 5 Thus, while (S)-1a has been previously described in the literature, 12 this is the first time the absolute stereochemistry of this compound has been definitively determined by X-ray diffraction. This procedure was successfully employed to determine the absolute stereochemistry of the novel enantiopure acids (S)-1b-1d.…”

“…4 As part of an on-going program of research into enantioselective biotransformations, we have been interested in determining the absolute stereochemistry of a series of substituted 3-arylbutanoic acids 1a-1d, obtained via enzymatic hydrolysis of the corresponding ethyl ester ( Figure 1). 5 The enantiopure products were isolated as liquids at room temperature. The enantioselectivity of the enzyme catalyzed reactions was investigated by chiral HPLC analysis, 5 and appropriate conditions to separate and quantify the enantiomers of 1a-1d were identified.…”

“…5 The enantiopure products were isolated as liquids at room temperature. The enantioselectivity of the enzyme catalyzed reactions was investigated by chiral HPLC analysis, 5 and appropriate conditions to separate and quantify the enantiomers of 1a-1d were identified. However, knowledge of absolute stereochemistry was necessary to determine the sense of enantioselection with each of the biocatalysts employed.…”

“…(±)-1a, (±)-1b, (±)-1c, (±)-1d, (S)-1a, (S)-1b, (S)-1c, (S)-1d were prepared according to the literature methods. 5 Grinding was undertaken using a mixer mill equipped with stainless steel 5 mL grinding jars and one 2.5 mm stainless steel grinding ball per jar. Powder diffraction experiments were performed using graphite monochromatized Cu-K radiation at room temperature.…”

Identification of an Esterase Isolated Using Metagenomic Technology which Displays an Unusual Substrate Scope and its Characterisation as an Enantioselective Biocatalyst

“…[1b,6b,19-20] Notably, from this previously completed screen the number of enzymes which processed the substrate decreased as the steric bulk of the β-substituent increased, Table 1. [19] Concurrently the number of enzymes exhibiting enantiodiscrimination also decreased. In particular, enzymatic hydrolysis of substrate 5 bearing a t-butyl substituent was extremely challenging, with only two of the previously screened commercial hydrolases showing activity.…”