Abstract
Optically active (R)-2-hydroxy-4-phenylbutanoate esters ((R)-HPBE) are key precursors for the production of angiotension-converting enzyme (ACE) inhibitors, which are important prescriptive drugs for preventing the formation of angiotensin II and lowering the blood pressure. The biocatalytic asymmetric reduction of ethyl 2-oxo-4-phenylbutanoate (OPBE) to (R)-HPBE with carbonyl reductases has several advantageous attributes, including high enantioselectivity, mild reaction condition, high catalytic efficiency, and environmental benignity. An increasing number of OPBE reductases have been discovered owing to the drastic achievements in genomics, screening and evolution technologies, and process engineering. The potential of (R)-HPBE production process has also been intensively evaluated. This review covers recent progress on the bioreductive preparation of (R)-HPBE, especially on various screening approaches for the identification of OPBE reductases and their characterization.
Highlights
Active secondary alcohols, especially hydroxyl acids or hydroxyl acid esters, are important compounds for introducing chiral elements to pharmaceuticals, agricultural pesticides, and other fine chemicals [1,2,3,4]. (R)-2hydroxy-4-phenylbutanoate esters (OPBE), one class of chiral alcohols, are important precursors for the production of serials of angiotensin-converting enzymes (ACE) inhibitors, generally named as pril drugs, possessing (S)-homophenylalanine moiety as pharmacophore [5,6,7]
Whereas inhibitors of ACE could prevent the formation of angiotensin II, decrease the blood pressure [8,9]
Numbers of methods have been developed for the preparation of (R)-HPBE, including chemical, enzymatic, and chemoenzymatic approaches
Summary
Especially hydroxyl acids or hydroxyl acid esters, are important compounds for introducing chiral elements to pharmaceuticals, agricultural pesticides, and other fine chemicals [1,2,3,4]. (R)-2hydroxy-4-phenylbutanoate esters (OPBE), one class of chiral alcohols, are important precursors for the production of serials of angiotensin-converting enzymes (ACE) inhibitors, generally named as pril drugs (benazepril, cilazapril, quinapril, and ramipril), possessing (S)-homophenylalanine moiety as pharmacophore [5,6,7]. Compared with classic chemical processes, the asymmetric reduction of OPBE into (R)-HPBE, or the reduction of 2-oxo-4phneylbutyrate (OPB) to (R)-2-hydroxy-4-phenylbutyrate [(R)-HPB] employing reductases and dehydrogenases (Figure 2) has several advantageous attributes, including high selectivity, high efficiency, mild reaction condition, and environmental friendless [24,25,26,27]. Several literatures on the biocatalytic asymmetric reduction for pharmaceuticals, protein engineering strategies for robust enzymes in chemical synthesis have been reviewed [28,29,30,31,32].
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