Promiscuous Behavior of Rhizomucor miehei Lipase in the Synthesis of N‐Substituted β‐Amino Esters

Abstract

A mild and efficient procedure for the aza-Michael addition of amines to acrylates by using lipases as catalysts is reported. Various lipases, mono-and bifunctional amines, alkyl acrylates, and reaction parameters were studied. Under the optimal conditions, Rhizomucor miehei lipase showed high selectivity. It catalyzed the formation of the Michael monoadduct as the only product in high yield and purity. Moreover,

Urea treated subtilisin as a biocatalyst for transformations in organic solvents

“…21 Catalytic promiscuity of enzymes has opened up further avenues for use of enzymes in biotransformations. 19,20,22 We also report the effect of urea treatment on a promiscuous activity of subtilisin. These results demonstrate the functional utility of urea treated subtilisin in diverse biotranformations.…”

“…20,22,[35][36][37][38] Aldol reaction between 4-nitrobenzaldehyde and acetone 21 was chosen as a promiscuous reaction for catalysis with both subtilisin and urea treated subtilisin (Scheme 4). Figure 6 shows the comparative behaviour of subtilisin and urea treated subtilisin in different media namely solvent free (wherein substrate acetone itself acted as the reaction media), ethanol and hexane [A control with just the urea in solvent free medium resulted in just 0.5% conversion (data not shown)].…”

Recent Advances in Biocatalytic Promiscuity: Hydrolase‐Catalyzed Reactions for Nonconventional Transformations

“…Rhizomucor miehei lipase (RML) has also efficiently promoted the aza‐Michael reaction between alkyl acrylates and alkylamines, alkanolamines and diamines, leading to the selective preparation of 22 N ‐substituted β‐amino esters in 45–100% yield . A few organic solvents were tested such as hexane, toluene and diisopropyl ether, their performances resulting highly dependent on the nature of the nucleophile.…”

A Single Lipase‐Catalysed One‐Pot Protocol Combining Aminolysis Resolution and Aza‐Michael Addition: An Easy and Efficient Way to Synthesise β‐Amino Acid Esters

“…1 H NMR (400 MHz, CDCl 3 ): δ 5 H),4.13 (q,J = 7.2 Hz,2 H), 3.77 (dd, J = 6.0 Hz, 1 H), 2.75-2.63 (m, J = 6.1 Hz, 2 H), 2.46 (dt, J = 3.1 Hz, 2 H), 1.74 (br., 1 H), 1.78-1.56 (m, J = 7.3 Hz, 2 H), 1.25 (t,J = 7.2 Hz,3 H),0.81 (t,J = 7.4 Hz,3 H) ppm. 1 H NMR (400 MHz, CDCl 3 ): δ 5 H),4.13 (q,J = 7.2 Hz,2 H), 3.77 (dd, J = 6.0 Hz, 1 H), 2.75-2.63 (m, J = 6.1 Hz, 2 H), 2.46 (dt, J = 3.1 Hz, 2 H), 1.74 (br., 1 H), 1.78-1.56 (m, J = 7.3 Hz, 2 H), 1.25 (t,J = 7.2 Hz,3 H),0.81 (t,J = 7.4 Hz,3 H) ppm.…”

“…[1] Chiral β-amino acid esters have also been used to construct peptidomimetic oligomers, which is of high interest in both medicinal chemistry and material science. One of the most important ways to obtain β-amino acid esters is through aza-Michael addition, [3] which is also a classical method to build a C-N bond between an amine and an α,β-unsaturated carbonyl compound. One of the most important ways to obtain β-amino acid esters is through aza-Michael addition, [3] which is also a classical method to build a C-N bond between an amine and an α,β-unsaturated carbonyl compound.…”