Chiral δ-iodo-γ-lactones derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal: chemoenzymatic synthesis and antiproliferative activity

Gładkowski, Witold; Skrobiszewski, Andrzej; Mazur, Marcelina; Gliszczyńska, Anna; Czarnecka, Marta; Pawlak, Aleksandra; Obmińska-Mrukowicz, Bożena; Maciejewska, Gabriela; Białońska, Agata

doi:10.1016/j.tetasy.2016.02.003

Cited by 14 publications

(23 citation statements)

References 51 publications

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“…The nucleophilic attack of an oxygen atom from carboxylate ion is highly stereospecific and goes from opposite sides of halonium ion. The steric consequences are the antiperiplanar orientations of C-X and C-O bonds [17,19,35,36] that determine configurations of two new stereogenic centers at C-1 and C-1' in the formed halolactones. The rigid structure of the cyclohexane ring as well as the presented lactonisation mechanisms allowed us to assign (1S,6S,1'R) configuration for halolactones 6a, 7a and 8a obtained from (S)-acid 5a (Scheme 4).…”

Section: Synthesis Of Halolactonesmentioning

confidence: 99%

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

et al. 2020

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Starting from 1-acetyl-1-cyclohexene, three enantiomeric pairs (ee ≥ 99%) of bicyclic δ-halo-γ-lactones with cyclohexane ring were obtained in five-step synthesis. The key stereochemical steps were lipase-catalyzed kinetic resolution of racemic 1-(cyclohex-1-en-1-yl) ethanol followed by transfer of chirality to ethyl 2-(2-ethylidenecyclohexyl) acetate in the Johnson–Claisen rearrangement. Synthesized halolactones exhibited antiproliferative activity towards canine B-cell leukemia cells (GL-1) and canine B-cell chronic leukemia cells (CLB70) and the most potent (IC50 18.43 ± 1.46 μg/mL against GL-1, IC50 11.40 ± 0.40 μg/mL against CLB70) comparable with the control etoposide, was (1R,6R,1′S)-1-(1′-chloroethyl)-9-oxabicyclo[4.3.0]nonan-8-one (8b). All halolactones did not have a toxic effect on erythrocytes and did not change the fluidity of membranes in the hydrophobic region of the lipid bilayer. Only weak changes in the hydrophilic area were observed, like the degree of lipid packing and associated hydration. The racemic halolactones were also tested for their antimicrobial properties and found to exhibit selectivity towards bacteria, in particular, towards Proteus mirabilis ATCC 35659.

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Section: Synthesis Of Halolactonesmentioning

confidence: 99%

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

et al. 2020

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“…This method allowed us to determine the enantiomeric composition of unreacted ester and produced alcohol (as ester derivative) in one Chiral Gas Chromatography (CGC) analysis. The described procedure was succesfully applied in our earlier studies on the transesterification of allyl alcohols [21,27].…”

Section: Resultsmentioning

confidence: 99%

“…Compounds with a 4-arylbut-3-en-2-ol system are valuable chiral synthons in the synthesis of different biologically active compounds, i.a. Verapamil [19], Baclofen [20], or β-aryl substituted lactones with antiproliferative activity [21]. Many studies concerning their kinetic resolution by transesterification [22][23][24][25] or hydrolysis [25,26] have been developed recently.…”

Section: Introductionmentioning

confidence: 99%

Application of Lecitase® Ultra-Catalyzed Hydrolysis to the Kinetic Resolution of (E)-4-phenylbut-3-en-2-yl Esters

Leśniarek¹,

Chojnacka²,

Gładkowski³

2018

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The possibility of using Lecitase® Ultra as a novel alternative biocatalyst for the kinetic resolution of model racemic allyl esters of (E)-4-phenylbut-3-en-3-ol: Acetate (4a) and propionate (4b) through their enantioselective hydrolysis was investigated. Reaction afforded (+)-(R)-alcohol (3) and unreacted (−)-(S)-ester (4a or 4b). Hydrolysis of propionate 4b proceeded with higher enantioselectivity than acetate 4a. (R)-Alcohol (3) with highest enantiomeric excess (93–99%) was obtained at 20–30 °C by hydrolysis of propionate 4b, while the highest optical purity of unreacted substrate was observed for (S)-acetate 4a (ee = 34–56%). The highest enantioselectivity was found for the hydrolysis of propionate 4b catalyzed at 30 °C (E = 38). Reaction carried out at 40 °C significantly lowered enantiomeric excess of produced alcohol 3 and enantioselectivity in resolution. Lecitase® Ultra catalyzed the enantioselective hydrolysis of allyl esters 4a,b according to Kazlauskas’ rule to produce (R)-alcohol 3 and can find application as a novel biocatalyst in the processes of kinetic resolution of racemic allyl esters.

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“…However, since a large variety of chiral esters possess the stereogenic center in the nucleophilic part of molecule, to extend the substrate scope and increase the usability of this enzyme in the asymmetric synthesis, we employed Lecitase™ Ultra for the biocatalytic resolution of racemic 4-arylbut-3-en-2-ol esters. In our working group, these alcohols are the subject of special interest as chiral precursors of the optically active lactones with antiproliferative activity [56,57]. Likewise, they have been used in the production of chiral drugs [58,59].…”

Section: Introductionmentioning

confidence: 99%

Free and Immobilized Lecitase™ Ultra as the Biocatalyst in the Kinetic Resolution of (E)-4-Arylbut-3-en-2-yl Esters

et al. 2020

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The influence of buffer type, co-solvent type, and acyl chain length was investigated for the enantioselective hydrolysis of racemic 4-arylbut-3-en-2-yl esters using Lecitase™ Ultra (LU). Immobilized preparations of the Lecitase™ Ultra enzyme had significantly higher activity and enantioselectivity than the free enzyme, particularly for 4-phenylbut-3-en-2-yl butyrate as the substrate. Moreover, the kinetic resolution with the immobilized enzyme was achieved in a much shorter time (24–48 h). Lecitase™ Ultra, immobilized on cyanogen bromide-activated agarose, was particularly effective, producing, after 24 h of reaction time in phosphate buffer (pH 7.2) with acetone as co-solvent, both (R)-alcohols and unreacted (S)-esters with good to excellent enantiomeric excesses (ee 90–99%). These conditions and enzyme were also suitable for the kinetic separation of racemic (E)-4-phenylbut-3-en-2-yl butyrate analogs containing methyl substituents on the benzene ring (4b,4c), but they did not show any enantioselectivity toward (E)-4-(4’-methoxyphenyl)but-3-en-2-yl butyrate (4d).

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Chiral δ-iodo-γ-lactones derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal: chemoenzymatic synthesis and antiproliferative activity

Cited by 14 publications

References 51 publications

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

Chemoenzymatic Synthesis of Enantiomeric, Bicyclic δ-Halo-γ-lactones with a Cyclohexane Ring, Their Biological Activity and Interaction with Biological Membranes

Application of Lecitase® Ultra-Catalyzed Hydrolysis to the Kinetic Resolution of (E)-4-phenylbut-3-en-2-yl Esters

Free and Immobilized Lecitase™ Ultra as the Biocatalyst in the Kinetic Resolution of (E)-4-Arylbut-3-en-2-yl Esters

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