TY - JOUR
T1 - Thermodynamically and Kinetically Controlled Reactions in Biocatalysis – from Concepts to Perspectives
AU - Marsden, Stefan R.
AU - Mestrom, Luuk
AU - McMillan, Duncan G.G.
AU - Hanefeld, Ulf
PY - 2019
Y1 - 2019
N2 - The enzymatic synthesis of esters and peptides is unfavoured in aqueous solvent systems due to competing hydrolysis. This can be overcome by using energy rich substrate analogues: elimination of a good leaving group temporarily establishes more favourable equilibrium conditions, allowing for (nearly) complete conversion. While kinetically controlled syntheses of esters and peptides in water are common knowledge in biocatalysis textbooks, the prevalence of kinetic control is less well known for other enzyme classes. Here, the general concepts of thermodynamic and kinetic control are illustrated at the example of the well-studied synthesis of β-lactam antibiotics and are shown to similarly also apply to other enzyme classes. Notably, the enzymatic synthesis of diastereomers shows the same characteristic energy profile as that of Diels-Alder reactions. This allows for the selective synthesis of different diastereomers under either thermodynamically or kinetically controlled conditions. Prospects and pitfalls of this notion are discussed at the example of the thermodynamic epimerisation of hydroxysteroids and recent examples of kinetically controlled aldol reactions. Kinetic reaction control can therefore not only be used to increase conversions towards a single product, but also to selectively afford different diastereomers. This review highlights the prevalence of both concepts within the field of biocatalysis.
AB - The enzymatic synthesis of esters and peptides is unfavoured in aqueous solvent systems due to competing hydrolysis. This can be overcome by using energy rich substrate analogues: elimination of a good leaving group temporarily establishes more favourable equilibrium conditions, allowing for (nearly) complete conversion. While kinetically controlled syntheses of esters and peptides in water are common knowledge in biocatalysis textbooks, the prevalence of kinetic control is less well known for other enzyme classes. Here, the general concepts of thermodynamic and kinetic control are illustrated at the example of the well-studied synthesis of β-lactam antibiotics and are shown to similarly also apply to other enzyme classes. Notably, the enzymatic synthesis of diastereomers shows the same characteristic energy profile as that of Diels-Alder reactions. This allows for the selective synthesis of different diastereomers under either thermodynamically or kinetically controlled conditions. Prospects and pitfalls of this notion are discussed at the example of the thermodynamic epimerisation of hydroxysteroids and recent examples of kinetically controlled aldol reactions. Kinetic reaction control can therefore not only be used to increase conversions towards a single product, but also to selectively afford different diastereomers. This review highlights the prevalence of both concepts within the field of biocatalysis.
KW - Asymmetric synthesis
KW - Biocatalysis
KW - Diastereomers
KW - Kinetic control
KW - Thermodynamic control
UR - http://www.scopus.com/inward/record.url?scp=85076750462&partnerID=8YFLogxK
U2 - 10.1002/cctc.201901589
DO - 10.1002/cctc.201901589
M3 - Review article
AN - SCOPUS:85076750462
SN - 1867-3880
VL - 12
SP - 426
EP - 437
JO - ChemCatChem
JF - ChemCatChem
IS - 2
ER -