Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis

Abstract

Oxazole compounds, including one nitrogen atom and one oxygen atom in a five-membered heterocyclic ring, are present in various biological activities. Due to binding with a widespread spectrum of receptors and enzymes easily in biological systems through various non-covalent interactions, oxazole-based molecules are becoming a kind of significant heterocyclic nucleus, which have received attention from researchers globally, leading them to synthesize diverse oxazole derivatives. The van Leusen reaction, based on tosylmethylisocyanides (TosMICs), is one of the most appropriate strategies to prepare oxazole-based medicinal compounds. In this review, we summarize the recent advances of the synthesis of oxazole-containing molecules utilizing the van Leusen oxazole synthesis from 1972, aiming to look for potential oxazole-based medicinal compounds, which are valuable information for drug discovery and synthesis.

Synthesis, In Silico and In Vitro Evaluation of Antimicrobial and Toxicity Features of New 4-[(4-Chlorophenyl)sulfonyl]benzoic Acid Derivatives

“…Given the biological importance of the final products of this work, namely of heterocyclic compounds from the class of 1,3-oxazoles, these compounds were obtained over time by a variety of synthetic methods [ 9 ]. Our multi-step synthesis strategy used a natural α-amino acid as the starting material and led to good yields of the newly synthesized compounds of the four chemical classes ( N -acyl-α-amino acids, 1,3-oxazol-5(4 H )-ones, N -acyl-α-amino ketones, 1,3-oxazoles), which were further characterized by physico-chemical methods and assessed for their antimicrobial and antibiofilm effects, toxicity on D. magna , and by in silico studies to predict their potential mechanism of action and toxicity.…”

“…The literature survey on the synthesized five-membered heterocycles with two heteroatoms from 1,3-oxazoles class highlighted that they are also endowed with a wide range of potent pharmacological activities [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ], such as antifungal, antibacterial (e.g., sulfaguanole with trade name: Enterocura, a sulfanilamide drug used for patients with acute diarrhea), anticancer (e.g., mubritinib), analgesic, antipyretic, anti-inflammatory (e.g., oxaprozin, a COX-2 inhibitor currently in the market, romazarit, the Roche candidate, which was withdrawn due to its toxicity profile), and anti-diabetic (e.g., darglitazone, an antihyperglycemic agent belonging to the glitazone class) effects. The structures of the representative bioactive synthetic compounds sharing the 1,3-oxazole scaffold are presented in Figure 2 .…”

“…Whereas the 1,3-oxazole moiety is a common heterocyclic motif identified in numerous natural products and biologically active synthetic molecules, over time the preparation of compounds from this class has attracted the attention of researchers who have reported many efficient chemical methods of synthesis. The most important synthetic strategies of 1,3-oxazoles include the reaction of aldehydes with tosylmethyl isocyanide (van Leusen synthesis), the Cornforth rearrangement, the condensation of aldehydes with cyanohydrins in the presence of hydrogen chloride (Fischer synthesis), the Doyle reaction of diazocarbonyl compounds with nitriles, the Robinson–Gabriel synthesis consisting of the intramolecular cyclodehydration of N -acyl-α-amino ketones, the Blümlein–Lewy method involving the condensation of α-halo or α-hydroxy ketones with primary amides, and the Dakin–West reaction of α-amino acids with acid anhydrides in the presence of a base, typically pyridine [ 9 , 17 , 18 ], etc. Recently, synthesis of the 2,5-polyfunctionalized 1,3-oxazole derivatives starting from acyl chlorides and propargyl amine via a consecutive amidation-coupling-isomerization sequence involving an in situ acyl Sonogashira cross-coupling was developed by Müller’s group [ 19 ].…”

Sustainable Access to 5‐Amino‐Oxazoles and Thiazoles via Calcium‐Catalyzed Elimination‐Cyclization with Isocyanides

“…Oxazoles play an increasingly important role in the discovery of new therapeutics, [10] from antibacterial agents targeting multiple ESKAPE pathogens [11] to novel kinase inhibitors for the treatment of cancer [12] . Unsurprisingly, much attention has been paid to their synthesis, including the classical Robinson‐Gabriel synthesis [13] and Van‐Leusen reaction [14] . More modern approaches using stoichiometric Lewis acids, [15] and redox strategies [16] have been successful in producing a range of substituted oxazoles.…”

Synthesis and Biological Evaluation of New N-Acyl-α-amino Ketones and 1,3-Oxazoles Derivatives

“…Among them, the synthetic heterocycles containing 1,3-oxazole nucleus have a wide range of biological activities, such as antimicrobial (e.g., sulfamoxole, a chemotherapeutic agent from the sulfonamides group) [ 1 , 2 ], anticancer (e.g., mubritinib, a tyrosine kinase inhibitor) [ 3 ], analgesic, antipyretic, anti-inflammatory (e.g., oxaprozin) [ 4 , 5 ], anti-diabetic (e.g., aleglitazar, a dual PPARα/γ agonist from glitazar class used in the treatment of type 2 diabetes) [ 6 ], antithrombotic (e.g., ditazole, an inhibitor of platelet aggregation) [ 7 ], and skeletal muscle relaxant (e.g., azumolene) [ 8 ] actions. The structures of the representative bioactive compounds sharing the 1,3-oxazole scaffold are presented in Figure 1 .…”