Facile synthesis of aminonaphthoquinone Mannich bases by noncatalytic multicomponent reaction

Mannich bases are formed in a noncatalytic multicomponent reaction, which is promoted by ultrasound irradiation. The procedure avoids the use of toxic solvents, catalyst, and purification, generating the desired compounds in excellent yields and short reaction times.     

Polyethylene Glycol (PEG 300) and Water–Ethanol as Benign Solvent Systems for the Synthesis of a Novel Series of 2-Hydroxynaphthalen-1(4H)-Ones

An improved, clean, simple, and efficient method for the synthesis of new series of 2-hydroxy-4-methylenenaphthalen-1(4H)-one is described. This new process involves a domino Michael addition of various methylene acid compounds with the sodium salt of 1,2-naphthoquinone-4-sulfonate either in basic (tBuOK) polyethylene glycol (PEG300) at room temperature or in a basic (NaOH) water–ethanol medium at 40 °C by a crushing in a mortar or a traditional heating.     

Chemoselective Synthesis of Mannich Adducts from 1,4-Naphthoquinones and Profile as Autophagic Inducers in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance. Thus, the development of new drugs becomes of great importance. Naphthoquinones have been described with antitumor activity. Some of them are found in nature, but semi synthesis has been used as strategy to find new chemical entities for the treatment of cancer. In the present study, we promote a multiple component reaction (MCR) among lawsone, arylaldehydes, and benzylamine to produce sixteen chemoselectively derivated Mannich adducts of 1,4-naphthoquinones in good yield (up to 97%). The antitumor activities and molecular mechanisms of action of these compounds were investigated in OSCC models and the compound 6a induced cytotoxicity in three different tumor cell lines (OSCC4, OSCC9, and OSCC25) and was more selective (IS > 2) for tumor cells than the chemotropic drug carboplatin and the controls lapachol and shikonin, which are chemically similar compounds with cytotoxic effects. The 6a selectively and significantly reduced the amount of cell colony growth, was not hemolytic, and tolerable in mice with no serious side effects at a concentration of 100 mg/kg with a LD₅₀ of 150 mg/kg. The new compound is biologically stable with a profile similar to carboplatin. Morphologically, 6a does not induce cell retraction or membrane blebs, but it does induce intense vesicle formation and late emergence of membrane bubbles. Exploring the mechanism of cell death induction, compound 6a does not induce ROS formation, and cell viability was not affected by inhibitors of apoptosis (ZVAD) and necroptosis (necrostatin 1). Autophagy followed by a late apoptosis process appears to be the death-inducing pathway of 6a, as observed by increased viability by the autophagy inhibitor (3-MA) and by the appearance of autophagosomes, later triggering a process of late apoptosis with the presence of caspase 3/7 and DNA fragmentation. Molecular modeling suggests the ability of the compound to bind to topoisomerase I and II and with greater affinity to hPKM2 enzyme than controls, which could explain the mechanism of cell death by autophagy. Finally, the in-silico prediction of drug-relevant properties showed that compound 6a has a good pharmacokinetic profile when compared to carboplatin and doxorubicin. Among the sixteen naphthoquinones tested, compound 6a was the most effective and is highly selective and well tolerated in animals. The induction of cell death in OSCC through autophagy followed by late apoptosis possibly via inhibition of the PKM2 enzyme points to a promising potential of 6a as a new preclinical anticancer candidate.     

Facile,One-Pot,Three-Component Synthesis of Benzo[a]naphthacene-8,13-diones

One-pot synthesis of 14-aryl-14H-7-oxa-benzo[a]naphthacene-8,13-diones was developed by the reaction of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and 2-naphthol in the presence of acetic acid. The structures of these compounds were identified by elemental analyses, infrared, ¹H NMR, and mass.     

A new lawsone azo-dye for optical sensing of Fe3+ and Cu2+ and their DFT study

A new lawsone-based azo-dye 2-hydroxy-3-((pyridin-2-ylmethyl)diazenyl)naphthalene-1,4-dione (1) was synthesized and applied for sensing of metal ions. Receptor 1 showed selective fluorescent and colorimetric response for the detection of Cu²⁺ and Fe³⁺ over other tested metal ions. The fluorescence intensity of 1 was significantly quenched allowing detection of Fe³⁺ and Cu²⁺ down to 0.61 and 6.06 μM, respectively. The binding has been established by fluorescence spectroscopic method. Receptor 1 provided a 1?:?1 binding scaffold for recognition of Fe³⁺ and Cu²⁺ ions with the association constant of 3.33 × 10⁶ and 3.33 × 10⁵ M^?1, respectively. The B3LYP/6-31G/LANL2DZ method was employed for the optimization of 1 and 1·Fe³⁺ and 1·Cu²⁺.     

Catalytic Asymmetric Synthesis of Benzobicyclo[3.2.1]octanes

Lawsone aldehydes were directly transformed into the biologically important, unique carbon skeleton of chiral methanobenzo[f]azulenes/methanodibenzo[a,d][7]annulenes in high dr and ee and in very good yields by using quinine-thiourea-catalyzed tandem Wittig/intramolecular Michael/intramolecular aldol reactions. This asymmetric catalytic tandem protocol will be highly useful because these final molecules are basic skeletons of important antibiotics.     

Fluorescence and surface-enhanced vibrational spectroscopies of lawsone and plumbagin

The natural dyes lawsone and plumbagin (1,4-naphthoquinones) were studied by using fluorescence, Raman, infrared (IR), surface-enhanced Raman scattering (SERS), and surface-enhanced IR absorption. From the absorption spectrum, it was possible to infer that the enol-lawsone tautomer concentration decreases in silver colloidal solution. Plumbagin dimers, both in water and in silver colloidal solution, were identified from the fluorescence band profile and surface-SERS spectrum. The SERS spectrum of lawsone was obtained by using silver colloidal solution after 12-hour settle; the keto and enol lawsone silver colloid interaction occurs. The assignment of Raman and IR bands of both dyes was calculated with density functional theory calculations. Only a monomeric structure of lawsone interacting with a silver cluster model was predicted. The monomer adopts a nearly coplanar orientation onto the silver surface; the shortest distance is 3.2 Å, suggesting an electrostatic interaction.     

One-Pot Synthesis of 2-Amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]chromene Derivatives Catalyzed by ZnCl2

An efficient one-pot synthesis of 2-amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]chromene derivatives has been achieved by the reaction of 2-hydroxynaphthalene-1,4-dione, cyanothioacetamide, and aromaticaldehyde in EtOH at room temperature catalyzed by ZnCl₂. The structures of the products were characterized by infrared, ¹H NMR, mass, and elemental analysis.

Parts-per-Million-Level,Catalytic [3+2]-Annulations for the Asymmetric Synthesis of Methanobenzo[7]annulenes

3-Alkyl-lawsones selectively reacted with α-alkyl-nitroethylenes under 500 parts-per-million (ppm) quinine-NH-thiourea-catalysis to furnish the chiral methanobenzo[7]annulenes in up to >99 % ee with >20 : 1 dr and TON up to 1820 through tandem Michael/Henry [3+2]-annulations. These asymmetric ppm-level, catalytic tandem [3+2]-annulations would be highly inspirational for the design of many more ppm-level organocatalytic reactions, and at the same time these final molecules are basic skeletons of antibiotics.