2-substituted Naphtho Research Articles

A facile access to 2-substituted naphtho[2,3-g]quinoline-3-carboxylic acid esters via intramolecular cyclization and PyBOP-promoted functionalization

Heteroarene-fused derivatives of anthraquinone (anthracene-9,10-dione) represent an exceptionally productive class for the search for new anticancer compounds with improved properties. In this study, we report a convenient heterocyclization, which in three steps leads to 2-alkyl-, aryl-, or hydroxyl derivatives of 5,12-dimethoxynaphtho[2,3-g]quinoline-3-carboxylic acid esters. The scheme includes an alkylation of CH-acids with 2-(bromomethyl)-1,4-dimethoxy-3-nitroanthraquinone (8) followed by reductive cyclization and oxidative aromatization. To increase the series of naphtho[2,3-g]quinoline derivatives, a mild and effective PyBOP-mediated functionalization was developed, which introduced N-, S-, and O-nucleophiles at the 2-position of the quinoline core. We believe that this study allows to access a broad family of 2-substituted naphtho[2,3-g]quinolines and can be adapted for other quinoline derivatives or polyaromatic analogs.

Microwave-assisted Synthesis of 2-Substituted Naphtho[1,2-d][1,3]oxazoles by Reacting 1-Nitroso-2-naphthol with Allyl Bromides and Benzyl Bromides using FeCl3 as Catalyst

Efficient and improved preparation of 2-substituted[1,2-d][1,3]oxazoles by the reaction of 1-nitroso-2-naphthol and allyl bromides, benzyl bromides under microwave condition utilizing FeCl3 as a catalyst with yield ranging from 32% to 72%. Reaction with bromo acetonitrile yields the corresponding 2-cyanonaphthoxazole with 58% yield.

Reaction of 1-Nitroso-2-naphthols with α-Functionalized Ketones and Related Compounds: The Unexpected Formation of Decarbonylated 2-Substituted Naphtho[1,2-d][1,3]oxazoles

Reactions between 1-nitroso-2-naphthols and α-functionalized ketones such as α-bromo-, α-chloro-, α-mesyloxy-, α-tosyloxy-, and α-hydroxy ketones under basic conditions delivered 2-substituted naphtho[1,2-d][1,3]oxazoles in a single synthetic operation. The product formation was accompanied by the unexpected loss of the C═O group from the α-functionalized ketones. With aryl bromides, allyl bromides, α-bromo diketones, α-bromo cyanides, α-bromoesters, and α-bromo ketoesters as substrates the formation of naphtho[1,2-d][1,3]oxazoles was also observed. The transformations were performed in 1,2-dichloroethane or acetonitrile under reflux and gave the corresponding naphthoxazoles with yields ranging between 52% and 85%.

Synthesis and Structure–Activity Relationships of Lapacho Analogues. 1. Suppression of Human Keratinocyte Hyperproliferation by 2-Substituted Naphtho[2,3-b]furan-4,9-diones, Activation by Enzymatic One- and Two-Electron Reduction, and Intracellular Generation of Superoxide

A series of linearly anellated lapacho quinone analogues substituted at the 2-position of the tricyclic naphtho[2,3-b]furan-4,9-dione system were synthesized and evaluated for their ability to suppress keratinocyte hyperproliferation using HaCaT cells as the primary test system. While very good in vitro potency with IC(50) values in the submicromolar range was attained with electron-withdrawing substituents, some compounds were found to induce plasma membrane damage, as evidenced by the release of LDH activity from cytoplasm of the keratinocytes. The most potent analogue against keratinocyte hyperproliferation was the 1,2,4-oxadiazole 18, the potency of which was combined with comparably low cytotoxic membrane damaging effects. Structure-activity relationship studies with either metabolically stable or labile analogues revealed that the quinone moiety was required for activity. Selected compounds were studied in detail for their capability to generate superoxide radicals both in isolated enzymatic one- and two-electron reduction assays as well as in a HaCaT cell-based assay.

ChemInform Abstract: Unexpected Reaction of 2‐Amino‐1,4‐naphthoquinone with Aldehydes: New Synthesis of Naphtho[2,1‐d]oxazole Compounds.

Abstract Treatment of 3-substituted 2-amino-1,4-naphthoquinones 3 with an aldehyde in a solution of hydrobromic acid in acetic acid led to 2,4-disubstituted naphtho[2,1-d]oxazol-5-ols. The outcome of this simple conversion is even more remarkable in view of the very similar reactions reported in literature, which all give rise to completely different products. Furthermore, the acquired naphthoxazoles 5–11 could be oxidatively ring opened by means of PIFA or CAN into a series of N-acylated 2-amino-1,4-naphthoquinones. A synthetic pathway towards 2-substituted naphtho[2,3-d]oxazole-4,9-diones was also disclosed as the outcome of CAN mediated oxidation of a 4-chloronaphtho[2,1-d]oxazol-5-ol.

Unexpected reaction of 2-amino-1,4-naphthoquinone with aldehydes: new synthesis of naphtho[2,1- d]oxazole compounds

Treatment of 3-substituted 2-amino-1,4-naphthoquinones 3 with an aldehyde in a solution of hydrobromic acid in acetic acid led to 2,4-disubstituted naphtho[2,1- d]oxazol-5-ols. The outcome of this simple conversion is even more remarkable in view of the very similar reactions reported in literature, which all give rise to completely different products. Furthermore, the acquired naphthoxazoles 5– 11 could be oxidatively ring opened by means of PIFA or CAN into a series of N-acylated 2-amino-1,4-naphthoquinones. A synthetic pathway towards 2-substituted naphtho[2,3- d]oxazole-4,9-diones was also disclosed as the outcome of CAN mediated oxidation of a 4-chloronaphtho[2,1- d]oxazol-5-ol.

Synthesis and Antitumor Evaluation of Thiophene Analogs of Kigelinone

The synthesis of kigelinone thiophene analogs and related naphtho[2,3-b]thiophene-4,9-quinones from 2- substituted 4,7-dimethoxybenzo[b]thiophenes via an oxidative deprotection, Diels-Alder, and oxidative aromatization reaction sequence is reported. The 2-substituted naphtho[2,3-b]thiophene-4,9-quinones display significant antitumor activity in the range IC50 1.1-47 μM on a panel of four distinct human cancer cell lines.

Cytotoxic Activity toward KB Cells of 2-Substituted Naphtho[2,3-b]furan-4,9-diones and Their Related Compounds

We investigated the cytotoxic activity of 2-substituted naphtho[2,3-b]furan-4,9-diones. We have previously synthesized 33 types of 2-substituted and related compounds, and the cytotoxic activity of these compounds was then examined by a KB cell culture assay. 2-(3-Furanoyl)benzoic acids and 1,4-naphthoquinones had no activity. 2-Acetyl-4,9-dimethoxynaphtho[2,3-b]furan 4 showed low activity. However, parent naphtho[2,3-b]furan-4,9-dione 2 and most 2-substituted derivatives exhibited cytotoxic activity. The parent structure was therefore for cytotoxicity. 2-Formylnaphtho[2,3-b]furan-4,9-dione 11 had particularly potent activity (ED50=0.09 microg/ml).

Gas-phase thermolysis of 1-acylnaphtho[1,8- de][1,2,3]triazines. Interesting direct routes towards condensed naphtho[1,8- de]heterocyclic ring systems

FVP pyrolysis of 1-acylnaphtho[1,8- de][1,2,3]triazines at 500 °C and 10 −2 Torr gave exclusively the corresponding 2-substituted naphtho[1,8- de][1,3]oxazines. The latter was also obtained by static pyrolysis but in lower yield along with the corresponding N-(naphthalen-1-yl)acylamides. The reaction was studied kinetically and mechanistically.

One-pot synthesis of naphtho[2,3- b]furan-4,9-diones by sequential coupling/ring closure reactions

Treatment of 3-phenyliodonio-1,2,4-trioxo-1,2,3,4-tetrahydronaphthalenides with terminal acetylenes in the presence of a bis(triphenylphosphine)palladium chloride-cuprous iodide catalyst or cuprous oxide in N-methylpiperidine or pyridine, respectively, furnished the corresponding 2-substituted naphtho[2,3- b]furan-4,9-diones in moderate to good yields. The utility of this method was demonstrated in the synthesis of a cytotoxic natural product, 2-(1-hydroxyethyl)naphtho[2,3- b]furan-4,9-dione.

The Simple Preparation of Aldehydes and Ketones by the Photo-Oxygen Rearrangement of Naphtho[1,8-de]dithiin Monooxides

Abstract Naphthalene-1,8-dithiol reacted with aldehydes to give dithioacetals which were oxidized to 2-substituted naphtho[1,8-de]1,3-dithiin-1-oxides (4). 2,2-Disubstituted naphtho[1,8-de]1,3-dithiin-1-oxides (5) were obtained on treatment of 4 with NaH/electrophiles. Photolysis of 4 and 5 undergoes intramolecular oxygen rearrangement to generate aldehydes and ketones quantitatively together with naphthalene-1,8-dithiole.

Synthesis of 2-substituted naphtho[2,3-f]isoquinoline-7, 12-dione N-oxides

1-Acetylenyl-2-formylanthraquinone oximes cyclize upon heating in an ethanol-water solution of K2CO3 to give 2-substituted naphtho[2,3-f]isoquinoline-7,12-dione N-oxides.

Convenient method for the synthesis of 2-substituted naphtho[2,3?g]indole-6,11-diones

A convenient one-step method has been developed for the preparation of 2-substituted naphtho[2,3- g]indole-6,11-diones entailing the addition of piperidine to 1-amino-2-acetylenylanthraquinone and subsequent cyclization of the adduct with loss of the amine in the presence of dilute hydrochloric acid.

A new route to naphtho[2,3-b]furan-4,9-diones from thio-substituted 1,4-naphthoquinones

Reaction of 2-phenylthio- or 2-ethylthio-1,4-naphthoquinones (1) and (2) with lithium enolates or pyridinium ylides was found to give alkylated 1,4-naphthoquinones (3)–(6) in high yields. Alkylated 1,4-naphthoquinones (5) and (6) were then effectively cyclized to 2-substituted naphtho[2,3-b]furan-4,9-diones (8) by action of bromine in acetic acid.

Über o-Hydroxyarylvinylpyryliumsalze—II

The properties of 2-substituted naphtho[1.2-b]pyrylium- and (1-hydroxy-2-naphthyl)vinylpyryliumsalts are reported, their behaviour is compared with that of the part I compounds.