Figure 4
Schematic representation depicting the investigated amines 1-4 and the bio-catalyzed asymmetric synthesis of cyanoacetamide (1a-4a) and methoxyacetamide (1b-4b).
Source publication
Cyanoacetamides are vital synthons in synthetic organic chemistry. However, methods to enantiopure cyanoacetamides have not yet been well explored. In this work, the preparation of cyanoacetamide synthons RS-(1a–4a) or methoxyacetamides RS-(1b–4b) in enantiopure/enriched form was investigated. Compounds S-1, S-2, R-1b, R-1a, andR-2b were prepared i...
Contexts in source publication
Context 1
... in these cases, the reaction should be ended early at the point when the fast-reacting enantiomer (in our case R-1a and R-2a) is as enantiopure as possible. The excellent baseline HPLC separations (Table 1 and Supplementary Materials Table S1) of amines 1-4 and amides 1a-4a and 1b-4b (Figure 4) maintained such precise and accurate following up and supported an evidence-based-reaction ending decision. ...
Context 2
... in these cases, the reaction should be ended early at the point when the fast-reacting enantiomer (in our case R-1a and R-2a) is as enantiopure as possible. The excellent baseline HPLC separations (Table 1 and Supplementary Materials Table S1) of amines 1-4 and amides 1a-4a and 1b-4b (Figure 4) maintained such precise and accurate following up and supported an evidence-based-reaction ending decision. Amine S-4 was also attainable but in low enantiopurity (ee 9%) via lipase-catalyzed cyanoacetamidation, while R-4a was accomplished in enantioenriched form with a good enantiomeric excess (ee 76%). ...
Context 3
... amides 1a/b-4a/b were prepared from the corresponding amines 1-4 (Figure 4) following the reported procedures [67]. Thus, ethyl 2-cyanoacetate or ethyl 2-methoxyacetate (0.001 mol) was added to a solution of 1-4 (0.001 mol) in toluene (2 mL) and stirred at room temperature for 72 h. ...
Citations
... However, like every other free enzyme, it can have several limitations, such as instability, nonreusability, and sensitivity to several reactants, which immobilization can circumvent [6]. The immobilized forms of this versatile biocatalyst have been used for the KR of chiral alcohols [7-10], azolides [11], and amines [12][13][14][15][16][17]. ...
In lipase-catalyzed kinetic resolutions (KRs), the choice of immobilization support and acylating agents (AAs) is crucial. Lipase B from Candida antarctica immobilized onto magnetic nanoparticles (CaLB-MNPs) has been successfully used for diverse KRs of racemic compounds, but there is a lack of studies of the utilization of this potent biocatalyst in the KR of chiral amines, important pharmaceutical building blocks. Therefore, in this work, several racemic amines (heptane-2-amine, 1-methoxypropan-2-amine, 1-phenylethan-1-amine, and 4-phenylbutan-2-amine, (±)-1a–d, respectively) were studied in batch and continuous-flow mode utilizing different AAs, such as diisopropyl malonate 2A, isopropyl 2-cyanoacetate 2B, and isopropyl 2-ethoxyacetate 2C. The reactions performed with CaLB-MNPs were compared with Novozym 435 (N435) and the results in the literature. CaLB-MNPs were less active than N435, leading to lower conversion, but demonstrated a higher enantiomer selectivity, proving to be a good alternative to the commercial form. Compound 2C resulted in the best balance between conversion and enantiomer selectivity among the acylating agents. CaLB-MNPs proved to be efficient in the KR of chiral amines, having comparable or superior properties to other CaLB forms utilizing porous matrices for immobilization. An additional advantage of using CaLB-MNPs is that the purification and reuse processes are facilitated via magnetic retention/separation. In the continuous-flow mode, the usability and operational stability of CaLB-MNPs were reaffirmed, corroborating with previous studies, and the results overall improve our understanding of this potent biocatalyst and the convenient U-shape reactor used.
... Many baseline enantioselective HPLC separations of amines 1-4, their cyanoacetamides (1a-4a), and methoxyacetamides (1b-4b) were achieved by utilizing diverse mobile-phase compositions and two cellulose-based CSPs (ODH ® and LUX-3 ® columns). Such enantioselective HPLC separations were used to monitor the lipase-catalyzed kinetic resolution of amines RS-(1-4) [29]. ...
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