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 Gudelis,
Sonata Krikštolaitytė,
Monika Stančiauskaitė,
Urtė Šachlevičiūtė,
Aurimas Bieliauskas,
Vaida Milišiūnaitė,
Rokas Jankauskas,
Neringa Kleizienė,
Frank A. Sløk,
Algirdas Šačkus
Affiliations
Emilis Gudelis
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Sonata Krikštolaitytė
Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania
Monika Stančiauskaitė
Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, LT-50254 Kaunas, Lithuania
Urtė Šachlevičiūtė
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Aurimas Bieliauskas
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Vaida Milišiūnaitė
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Rokas Jankauskas
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Neringa Kleizienė
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
Frank A. Sløk
Vipergen ApS, Gammel Kongevej 23A, V DK-1610 Copenhagen, Denmark
Algirdas Šačkus
Institute of Synthetic Chemistry, Kaunas University of Technology, K. Baršausko g. 59, LT-51423 Kaunas, Lithuania
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.
