Regioselective synthesis of methyl 5-(<i>N</i>-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

Bruzgulienė, Jolita; Račkauskienė, Greta; Bieliauskas, Aurimas; Milišiūnaitė, Vaida; Dagilienė, Miglė; Matulevičiūtė, Gita; Martynaitis, Vytas; Krikštolaitytė, Sonata; Sløk, Frank A.; Šačkus, Algirdas

doi:10.3762/bjoc.18.11

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…As expected, the 15 N chemical shifts of the N-1 Boc-azetidine (δ −315.0 ppm) and N-1′ azetidine (δ −350.2 ppm) atoms were highly comparable to those of compound 4a . The observed chemical shifts of the azetidine derivatives were consistent with the data reported in the literature [ 23 , 24 , 58 , 59 ].…”

Section: Resultssupporting

confidence: 90%

“…5-Aminopentanoic acid is a naturally occurring amino acid and a methylene homologue of GABA [ 22 ]. Recently, we developed efficient protocols that provide easy access to highly functional heterocyclic compounds by combining heterocyclic moieties with both carboxylic ester functional groups and cycloaminyl units, such as the δ-amino esters azetidine derivatives XII and XIII [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of New Azetidine and Oxetane Amino Acid Derivatives through Aza-Michael Addition of NH-Heterocycles with Methyl 2-(Azetidin- or Oxetan-3-Ylidene)Acetates

et al. 2023

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In this paper, a simple and efficient synthetic route for the preparation of new heterocyclic amino acid derivatives containing azetidine and oxetane rings was described. The starting (N-Boc-azetidin-3-ylidene)acetate was obtained from (N-Boc)azetidin-3-one by the DBU-catalysed Horner–Wadsworth–Emmons reaction, followed by aza-Michael addition with NH-heterocycles to yield the target functionalised 3-substituted 3-(acetoxymethyl)azetidines. Methyl 2-(oxetan-3-ylidene)acetate was obtained in a similar manner, which was further treated with various (N-Boc-cycloaminyl)amines to yield the target 3-substituted 3-(acetoxymethyl)oxetane compounds. The synthesis and diversification of novel heterocyclic amino acid derivatives were achieved through the Suzuki–Miyaura cross-coupling from the corresponding brominated pyrazole–azetidine hybrid with boronic acids. The structures of the novel heterocyclic compounds were confirmed via 1H-, 13C-, 15N-, and 19F-NMR spectroscopy, as well as HRMS investigations.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Synthesis of New Azetidine and Oxetane Amino Acid Derivatives through Aza-Michael Addition of NH-Heterocycles with Methyl 2-(Azetidin- or Oxetan-3-Ylidene)Acetates

et al. 2023

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“…The 13 C-15 N spin-spin interaction was observed for the signals of the major regioisomer C-3 ( 1 J C3 -N2 = 2.89 Hz), C-4 ( 2 J C4 -N2 = 1.23 Hz) and C-5 ( 2 J C5 -N2 = 1.39 Hz) from the 1,2-oxazole moiety, as well as the 2 J CN and 3 J CN couplings from the adjacent phenyl ring. The minor regioisomer provided similar data, where the 1 J CN coupling constants were higher than 2 J CN coupling constants, C-3 ( 1 J C3 -N2 = 2.25 Hz), C-4 ( 2 J C4 -N2 = 1.11 Hz), and C-5 ( 2 J C5 -N2 = 1.52 Hz) in the 1,2-oxazole moiety, which is in good agreement with the data reported in the literature [73]. Moreover, the 2 J CN and 3 J CN couplings were observed for the signals from the pyrazole fragment.…”

Section: General Informationsupporting

confidence: 92%

Synthesis and Characterization of Novel Heterocyclic Chalcones from 1-Phenyl-1H-pyrazol-3-ol

et al. 2022

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An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1H-pyrazol-3-ols bearing a formyl or acetyl group on the C4 position of pyrazole ring, employing a base-catalysed Claisen–Schmidt condensation reaction, is described. Isomeric chalcones were further reacted with N-hydroxy-4-toluenesulfonamide and regioselective formation of 3,5-disubstituted 1,2-oxazoles was established. The novel pyrazole-chalcones and 1,2-oxazoles were characterized by an in-depth analysis of NMR spectral data, which were obtained through a combination of standard and advanced NMR spectroscopy techniques.

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“…[40] In our recent work, we have been pursuing the construction of amino acid-like functionalized heterocyclic molecules possessing azetidine core. [41][42][43][44] In this study, we prepared a library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives, assessed their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and determined their neuroprotective effect in salsolinol (SAL)-induced model of PD and glutamate (Glu)-induced model of oxidative damage on neuron-like SH-SY5Y cells. Consequently, cholinesterase inhibition, alongside neuroprotective effect in Gluinduced Xc-antiporter inhibition models could offer a new strategy for disease-modifying AD and PD therapy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Šachlevičiūtė,

Gonzalez,

Kvasnicová

et al. 2023

Archiv der Pharmazie

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A library of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives was prepared from N‐Boc‐3‐azetidinone employing the Horner‐Wadsworth‐Emmons reaction, rhodium(I)‐catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N‐unprotected hydrochlorides, N‐alkylated and N‐acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol‐induced) and aspects of Alzheimer's disease (glutamate‐induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol‐ and glutamate‐induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase‐3/7 activity.

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Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

Cited by 6 publications

References 47 publications

Synthesis of New Azetidine and Oxetane Amino Acid Derivatives through Aza-Michael Addition of NH-Heterocycles with Methyl 2-(Azetidin- or Oxetan-3-Ylidene)Acetates

Synthesis of New Azetidine and Oxetane Amino Acid Derivatives through Aza-Michael Addition of NH-Heterocycles with Methyl 2-(Azetidin- or Oxetan-3-Ylidene)Acetates

Synthesis and Characterization of Novel Heterocyclic Chalcones from 1-Phenyl-1H-pyrazol-3-ol

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

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