Stereoselective Synthesis of Dipeptidyl Peptidase‐4 (DPP‐4) Inhibitor, (R)‐Sitagliptin

Abstract

An operationally simple and efficient strategy for a highly potent Dipeptidyl Peptidase-4 (DPP-4) inhibitor, sitagliptin has been developed employing readily available precursors. The chiral b-amino acid core of sitagliptin has been constructed through a Barbier type allylation of chiral sulfinyl imine or a Mannich type addition of diethyl malonate. This approach is more convenient, exquisitely selective and practical.

Promoter engineering‐mediated Tuning of esterase and transaminase expression for the chemoenzymatic synthesis of sitagliptin phosphate at the kilogram‐scale

“…Similarly, in our previous study, we developed a cascade reaction to convert β‐keto ester substrate (140 mM) into tfhe desired sitagliptin intermediate (82% conv., > 99% e.e ), using a commercial Candida rugosa lipase (CRL) for the hydrolysis of ester substrate, and TA from Ilumatobacter coccineus (TAIC) for subsequent amination of the corresponding β‐keto acid (G. H. Kim et al, 2019). It is worth noticing that this efficient strategy could be used to produce various β‐amino acids and also for the preparation of other gliptin derivatives such as retagliptin and evogliptin (Anjibabu et al, 2016).…”

Novel Approach for the Isolation and Immobilization of a Recombinant Transaminase: Applying an Advanced Nanocomposite System

“…[10] In recent years, the application of transaminases (TAs) has gained interest as promising biocatalysts that provide an environmentally friendly route for the synthesis of pharmaceutically relevant chiral amines with high stereoselectivity and catalytic turnover. [11][12][13] The ω-TAs are the most common natural enzymes that can directly synthesize enantiopure chiral amines by asymmetric amination of prochiral ketones or by kinetic resolution of the racemic mixture of amines. [14] Purification processes in protein engineering have a crucial role to obtain pure recombinant enzymes with high-level activity.…”

“…This makes them a commonly used marker in the diagnostics of liver and other gastrointestinal diseases [10] . In recent years, the application of transaminases (TAs) has gained interest as promising biocatalysts that provide an environmentally friendly route for the synthesis of pharmaceutically relevant chiral amines with high stereoselectivity and catalytic turnover [11–13] . The ω‐TAs are the most common natural enzymes that can directly synthesize enantiopure chiral amines by asymmetric amination of prochiral ketones or by kinetic resolution of the racemic mixture of amines [14] …”