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.

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 (-Boc-azetidin-3-ylidene)acetate was obtained from (-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 (-Boc-cycloaminyl)amines to yield the target 3-substituted 3-(acetoxymethyl)oxetane compounds.

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

An efficient synthetic route to construct diverse pyrazole-based chalcones from 1-phenyl-1-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 -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.

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

A convenient and efficient synthesis of novel achiral and chiral heterocyclic amino acid-like building blocks was developed. Regioisomeric methyl 5-(-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates were prepared by the reaction of β-enamino ketoesters (including azetidine, pyrrolidine or piperidine enamines) with hydroxylamine hydrochloride. Unambiguous structural assignments were based on chiral HPLC analysis, H, C, and N NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data.

Convenient Synthesis of Pyrazolo[4',3':5,6]pyrano[4,3-][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition.

A simple and efficient synthetic route to the novel 3a,4-dihydro-3,7- and 4,7-pyrazolo[4',3':5,6]pyrano[4,3-][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant isomer. The structures of the obtained heterocyclic products were confirmed by detailed H, C and N NMR spectroscopic experiments and HRMS measurements.

Synthesis and Characterization of Novel Methyl (3)5-(-Boc-piperidinyl)-1-pyrazole-4-carboxylates.

Series of methyl 3- and 5-(-Boc-piperidinyl)-1-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their -Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and ()- and ()-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with ,-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various -mono-substituted hydrazines afforded the target 5-(-Boc-piperidinyl)-1-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further -alkylated with alkyl halides to give 3-(-Boc-piperidinyl)-1-pyrazole-4-carboxylates.

Synthesis and anthelmintic activity of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives.

A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C.

Synthesis of 2-furo[2,3-]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction.

Fused pyrazole ring systems are common structural motifs of numerous pharmaceutically important compounds. Nevertheless, access to derivatives of the aromatic 2-furo[2,3-]pyrazole ring system is still quite limited, and their chemistry and functional properties remain largely underexplored. The current study investigates routes to construct this system from easily accessible starting materials using metal-catalyzed reactions.

Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines.

An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3-c]pyridines, which were then evaluated for their cytotoxicity against K562 and MCF-7 cancer cell lines.