14918-69-5Relevant academic research and scientific papers
A convenient synthesis of 2-formyl-1,8:4,5-bis(methylenedioxy) naphthalene
Zhao, Ai-Hong,Xu, De-Feng,Zhuo, Wen,Rao, Zhen,Li, Shao-Shun
, p. 647 - 648 (2007)
2,3-Dihydronaphazarin was prepared from 1,4-dimethoxybenzene and dichloromaleic anhydride. Reaction with bromochloromethane gave 1,8:4,5-bis(methylenedioxy)naphthalene which with NBS, gave 2-bromo-1,8:4,5-bis- (methylenedioxy)naphthalene. Reaction of the Grignard derivative with DMF afforded 2-formyl-1,8:4,5-bis(methylenedioxy)naphthalene. This method had several advantages compared with the reported synthesis, including fewer steps, milder condition and higher yields.
SYNTHETIC STUDIES ON NOGALAMYCIN CONGENERS ; CHIRAL SYNTHESIS OF THE CDEF-RING SYSTEM OF NOGALAMYCIN
Kawasaki, Motoji,Matsuda, Fuyuhiko,Terashima, Shiro
, p. 5713 - 5726 (1988)
The chiral synthesis of the (+)-naphthoquinone (4), the CDEF-ring system of nogalamycin congeners, has been accomplished following the synthetic scheme developed for the model (-)-DEF-ring system (3) in the preceding paper.This synthesis features (1) stereoselective construction of the C5'-asymmetric center by introducing the naphthalene moiety into the (-)-methyl ketone (5), the glycoside part, (2) regioselective oxidation of the 1,4,5,8-tetramethoxynaphthalene moiety with cerium(III) ammonium nitrate, and (3) efficient formation of bicyclic acetal system.
A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells
Bao, Xia-Zhen,Wang, Qi,Ren, Xiao-Rong,Dai, Fang,Zhou, Bo
, p. 597 - 608 (2020)
Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (H2O2)-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the H2O2-mediated conversion of boronate to free phenol. The boronate-protected Nap (PNap) can exploit increased levels of H2O2 in HepG2 cells to in situ release Nap followed by its efflux via conjugation with reduced glutathione (GSH), allowing that the Nap-GSH adduct works as a Cu(II) ionophore to induce continuously GSH depletion via a reduction-dependent releasing of Cu(I) by GSH. This strategy endows PNap with the unprecedented ability to hit multi-redox characteristics (increased levels of H2O2, GSH and copper) of HepG2 cells, leading to ROS generation preferentially in HepG2 cells along with their selective death.
Discovery of 1,4-Naphthoquinones as a New Class of Antiproliferative Agents Targeting GPR55
Badolato, Mariateresa,Carullo, Gabriele,Caroleo, Maria Cristina,Cione, Erika,Aiello, Francesca,Manetti, Fabrizio
, p. 402 - 406 (2019)
A new series of 1,4-naphthoquinones, bearing various cyclic and aliphatic amines on C2, was designed and synthesized to identify antiproliferative agents for triple-negative breast cancer, which represents a clinical challenge without targeted therapies. Among naphthoquinones, 2a and 3a inhibited the proliferation of MDA-MB-231 cells (EC50 = 1.6 and 2.7 μM, respectively), compared to primary human breast cells MCF10A. Furthermore, they did not affect the viability of peripheral blood mononuclear cells (PBMC), suggesting their potential safer use for cancer treatment. Recently, correlations have emerged between the expression of G protein-coupled receptor 55 (GPR55) and both triple-negative breast cancer development and invasion, making it a promising target for the development of targeted therapies. Based on this evidence, molecular docking studies supported the hypothesis of binding to GPR55, and pharmacological tests suggested that compound 3a could exert its antiproliferative activity acting as a GPR55 inverse agonist.
Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study
Sánchez-Calvo, Juan M.,Barbero, Gara R.,Guerrero-Vásquez, Guillermo,Durán, Alexandra G.,Macías, Mariola,Rodríguez-Iglesias, Manuel A.,Molinillo, José M. G.,Macías, Francisco A.
, p. 1274 - 1285 (2016)
The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16?μg/mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2?μg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal.
PROTEIN KINASE INHIBITORS AND USE THEREOF FOR TREATMENT OF NEIMODEGENERATIVE DISEASES
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Paragraph 0045; 0092, (2021/04/30)
The present disclosure relates to compounds that act as protein kinase inhibitors, especially CK1δ and/or CK1ε inhibitors, which can be used to treat a serine/threonine kinase-dependent disease and condition, such as neurodegenerative diseases like Alzheimer's Disease, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for neurodegenerative diseases, including Alzheimer's disease.
First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano-γ-lactone: (+)-γ-Actinorhodin
Neumeyer, Markus,Brückner, Reinhard
supporting information, p. 3383 - 3388 (2017/03/17)
We have accomplished the first total synthesis of an isomerically pure naphthoquinonopyrano-γ-lactone dimer, γ-actinorhodin, in eleven steps. Two steps exploit pairs of peri-MeO groups as unusual selectivity controls. The respective MeO groups convey the steric bulk of a bromo or iodo substituent located ortho to one MeO group as steric hindrance into the vicinity of the second MeO group. This relay effect was indispensable for exerting regiocontrol in an aromatic bromination and diastereocontrol in an oxa-Pictet–Spengler cyclization. The absolute configuration of our target compound was established in an asymmetric Sharpless dihydroxylation of a β,γ-unsaturated ester, which was synthesized in a Heck coupling of a bromoiodonaphthalene with ethyl vinylacetate. The dihydroxylation provided the γ-hydroxylactone moiety of the bromonaphthalene that was used as the substrate in the oxa-Pictet–Spengler cyclization. Dimerization to the core of γ-actinorhodin occurred by two Suzuki couplings.
Synthesis of Spinochrome D, A Metabolite of Various Sea-Urchin Species
Balaneva,Shestak,Anufriev,Novikov
, p. 213 - 217 (2016/07/06)
The sea-urchin metabolite spinochrome D (1) was synthesized in 58% overall yield via oxidation of 2,3-dichloronaphthazarin (13) into 2-hydroxy-6,7-dichloronaphthazarin (14), O-methylation of 14, nucleophilic substitution by MeO groups of the Cl atoms in the resulting 2-methoxy-6,7-dichloronaphthazarin (19), and hydrolysis of the obtained 2,3,6-trimethoxynaphthazarin (10).
Cycloacylation of chloro-substituted hydroquinone dimethyl ethers with dichloromaleic anhydride
Novikov,Balaneva,Shestak,Anufriev, V. Ph.,Glazunov
, p. 993 - 1003 (2017/01/11)
Under the drastic conditions of Zahn—Ochwat cycloacylation of 2-chloroand 2,3-dichlorohydroquinones with dichloromaleic anhydride (a melt of anhydrous AlCl3 and NaCl, 185—195 °C), the substrates undergo various degrees of disproportionation, which reduces the yields of the target triand tetrachloronaphthazarins. Quantum chemical calculations showed that the cycloacylation in question proceeds as a double aromatic electrophilic substitution of the vicinal protons with the corresponding oxocarbenium ions (acylium cations).
Practical first total synthesis of the potent phytotoxic (±)-naphthotectone, isolated from tectona grandis
Guerrero-Vasquez, Guillermo A.,Andrade, Carlos Kleber Z.,Molinillo, Jose M. G.,MacIas, Francisco A.
supporting information, p. 6175 - 6180 (2013/09/24)
Naphthotectone is a quinone isolated recently from teak extracts of Tectona grandis. It has been shown to be one of the most abundant compounds and the most active compound isolated form teak. Thus, it has been proposed that naphthotectone is one of the compounds responsible for the allelophathic activity of this plant. An efficient total synthesis of (±)- naphthotectone was achieved in seven steps and 31 % overall yield. The best results were obtained by using an aqueous Wittig reaction as a key step. Other reactions used were the formation of an epoxide ring by the Corey-Chaykovsky method, and an innovative one-pot anodic electrooxidation and demethylation. An efficient total synthesis of (±)-naphthotectone was achieved in seven steps and 31 % overall yield. This natural product has been proposed as one of the compounds responsible for the allelopathic activity of Tectona grandis. The synthetic route includes an aqueous Wittig olefination, a Corey-Chaikovsky epoxidation, and an innovative one-pot anodic electrooxidation and demethylation.
