Lipase-catalysed direct Mannich reaction in water: utilization of biocatalytic promiscuity for C–C bond formation in a “one-pot” synthesis

Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives

“…Kun Li et al previously demonstrated that the presence of water in the reaction media strongly influence the activity of lipases in the Mannich type condensation. In their experiments, the optimal water concentration was found to be between 40% and 50% [14]. Based on these reported data and taking into consideration the low solubility of heterocyclic aldehydes in water, we choose an acetone/water 1:1 (v/v) system as the reaction media, in order to increase the solubility of substrates.…”

“…-4-(2-phenylthiazol-4-yl) 89, 170.59, 167.23, 155.74, 140.24, 133.67, 130.05, 129.94, 129.29, 128.97, 128.43, 126.52, 116.90, 51.62, 45.81, 30.28, 23.60 02, 170.69, 167.56, 155.65, 138.78, 133.65, 130.92, 130.01, 129.33, 128.92, 128.47, 127.19, 123.78, 119.96, 116.83, 51.74, 45.89, 30.30, 23.64, 21.51. GC-MS: m/z found: 378 (M calculated for C22H22N2O2S: 378); m/z (%) = 379 (M + 1, 0.2), 378 (M, 1), 335 (14), 293 (24), 279 (6), 202 (11), 149 (2), 135 (5), 118 (8), 93 (12), 77 (10), 43 (100), 39 (10). -4-(2-p-tolylthiazol-4-yl) J = 23.7,16.5,11.5 Hz,2H),6.45 (t,J = 7.5 Hz,1H),3.10 (ddd,J = 24.6,16.5,7.5 Hz, 2H), 2.38 (s, 3H), 2.14 (s, 3H), 1.80 (s, 3H).…”

“…Previous studies reported that, besides their natural role, lipases are able to catalyze different synthetic reactions, such as C-C and C-N bond forming [13]. The lipase-catalyzed direct Mannich reaction using as substrates some substituted benzaldehydes, primary amines and ketones was previously described and a possible mechanism was also proposed [14]. The method afforded Mannich bases that cannot be obtained by classical Mannich reaction.…”

Diastereoselective synthesis of novel 2,5-dioxopyrrolidine derivatives via biocatalytic domino reactions

“…Mannich reactions, 29 Markovnikov reactions, Michael addition, 30 Diels-Alder reactions, 31 and some other domino reactions. Recently, Wang et al reported a novel lipase-catalyzed direct three-component reaction.…”

An Eco-Friendly Protocol for Synthesis of β- aminoketones via Mannich Reaction Using Citric Acid: A Biodegradable Catalyst

“…β-amino carbonyl derivatives are found in a number of biologically active natural products [5]. The reported Mannich reactions have been catalyzed by various Lewis or Brønsted acid catalysts such as silica-supported AlCl 3 [6], CeCl 3 .7H 2 0 [7], NbCl 5 [8], BiCl 3 [9], CAN [10], HClO 4 -SiO 2 [11], Bi(OTf) 3 [12], Zn(OTf) 2 [13], ionic liquid [14][15][16][17], sulphamic acid [18][19][20], Fe(Cp) 2 PF 6 [21], Cu-nanoparticles [22], [RE(PFO) 3 ] [23], silica based tin(II) catalyst [24], PEG-SO 3 H [25] ZSM-5-SO 3 H [26], carbon based solid acid [27], polyaniline/SiO 2 [28], lipase [29], saccharose [30], heteroplyacid salts [31]. However, most of the reported methods for the Mannich reaction suffer from drawbacks such as long reaction times and harsh reaction conditions, toxicity, and difficulty in product separation, which limit its use in the synthesis of complex molecules.…”