Design, synthesis and biological evaluation of novel α-acyloxy carboxamides via Passerini reaction as caspase 3/7 activators

4-(N-Phthalimido)phenyl Isonitrile as a Novel Convertible Isocyanide Analogue with the Odorless Property as an Extra Bonus

“…Thus, the reported bands were assigned to HOMO → LUMO via π−π* excitation (Figure 2). Moreover, the Passerini reaction 4 using the new isonitrile 9 was carried out using excess cyclohexanone 6 and o-nitrobenzoic acid, affording the corresponding Passerini product αacyloxy carboxamide 12, Scheme 2. The structure of 12 was confirmed by the 1 H NMR spectrum, Figure S11, where N−H amide appears as a singlet at δ H = 9.84 ppm; the 13 C NMR spectrum, Figure S12, shows three characteristic peaks for C� O groups of esters, phthalimido, and amide at δ C = 170.6, S13, shows absorption bands at 3392 cm −1 for NH amide and at 1738 and 1708 cm −1 for CO. Deprotection of the Pht group of α-acyloxy carboxamide 12 via hydrazinolysis gave 13 that possessed the expected free primary aromatic amine group and the tertiary alcohol.…”

“…The isocyanide group shows intermediate behavior between carbene and triple bond character, with a high degree of reactivity. Despite the undeniable role of isonitriles in organic synthesis and atom economy in many recorded MCRs, such as the Passerini three-component reaction (P-3CR) , and Ugi four-component reaction (U-4CR), , for the synthesis of pharmaceuticals, natural products, and perplexing organic compounds, , the overpowering stink of isonitriles severely limits their use, and one can say that in the realm of stinkers isonitriles may have no contender. Therefore, most researchers around the world have banned the use of isonitriles in their laboratories.…”

Immobilized Sulfuric Acid on Silica Gel as Highly Efficient and Heterogeneous Catalyst for the One-Pot Synthesis of Novel α-Acyloxycarboxamides in Aqueous Media

“…An excessive amount of catalyst may obstruct conversion due to catalyst poisoning caused by an excessive amount of reactants adhering to the catalyst surface. The amount of catalyst determines the availability of acidic sites, which when present in excess, may produce undesirable byproducts or promote the occurrence of the reversible reaction [ 28 ]. When the reaction was carried out in the presence of silica gel (without catalyst) the Passerini adducts were obtained in 64% yield within 15 min, which implies that the reaction rate depends greatly on the catalyst used.…”

“…This may be attributed to the planarity of the phenyl ring preventing the second Passerini reaction due to steric hindrance. According to a literature review, succinic acid could be used to synthesize bis α-acyloxycarboxamides [ 28 ]. The free rotation of the C-C bond between the two methylene groups was suggested as a strategy to increase the flexibility and avoid steric restriction around the -COOH.…”

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…In 2019, Ayoup et al [ 121 ] reported a new series of Passerini products, which were synthesized and evaluated as potent caspase-dependent apoptotic inducers. A series of α-acyloxy carboxamides was prepared from p-nitrophenyl isocyanide, cyclohexanone and various carboxylic acids, and the principal amide-based scaffold was decorated by diverse substituents in good yield ( Scheme 4 ).…”