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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.

Emilis GudelisSonata KrikštolaitytėMonika StančiauskaitėUrtė ŠachlevičiūtėAurimas BieliauskasVaida MilišiūnaitėRokas JankauskasNeringa KleizienėFrank A SløkAlgirdas Šačkus
Published in: Molecules (Basel, Switzerland) (2023)
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 1 H-, 13 C-, 15 N-, and 19 F-NMR spectroscopy, as well as HRMS investigations.
Keyphrases
  • amino acid
  • molecular docking
  • structure activity relationship
  • room temperature
  • high resolution
  • molecular dynamics simulations
  • solid phase extraction