Phenanthridine Skeleton Research Articles

Investigation of the reaction of 2- (2-aminophenyl)furan with maleic anhydride

Phenanthridinone derivatives have long been used as anticancer, antileukemic, antitumor, antiviral, antimicrobial, antifungal, antimalarial, and anti-irritant drugs. Despite several methods for the synthesis of phenanthridinone derivatives, flexible and versatile methodologies to construct phenanthridinones are still desirable. An intramolecular Diels-Alder reaction was used to construct the phenanthridine skeleton. The starting material was 2-(2-aminophenyl)furan. 2-(2-Аminophenyl)furan was obtained by arylation of furan with 2-nitrophenyldiazonium chloride followed by reduction of the nitro group with sodium borohydride in the presence of nickel chloride hexahydrate. The amine was acylated with maleic anhydride in benzene at room temperature. The formation of the Diels-Alder reaction adduct occurs when maleinimide 2-(2-aminophenyl) furan is heated in dioxane. During heating, the oxacycloheptene moiety is cleaved. And as a result, the oxabicycloheptene fragment is flavored to form 6-hydroxyphenanthridine-7-carboxylic acid. This reaction is confirmed by chromato-mass spectrometry. It is also interesting that when maleinimide 2-(2-aminophenyl) furan is heated in benzene it's leads to the formation of dark-colored resinous products.It is known that such intramolecular cycloadditions involving the furan ring occur with the formation of exo-adducts of the Diels-Alder reaction. In our opinion, the cis-placement of the carboxyl group and the bridging oxygen atom promotes easy proton migration with the opening of oxabicycloheptene. It should also be noted that in solution the Diels-Alder reaction product is in phenanthridinone tautomeric form. Proof of this is the signal of the hydrogen atom of the hydroxy group at 12.83 ppm and NH group proton at 11.76 ppm in the H 1 NMR spectrum of the obtained compound. Keywords: furan derivatives, 2-arylfurans, tandem cyclizations, phenanthridines

Palladium-catalyzed arylation of 1,4-naphthoquinones with aryl iodides and its synthetic application to the benzo[b]phenanthridine skeleton

We report a Pd-catalyzed arylation of 1,4-naphthoquinones with aryl iodides. This reaction shows excellent functional group tolerance and high regioselectivity when using nonsymmetric 1,4-naphthoquinone. Furthermore, the resulting 2-aryl-1,4-naphthoquinone could be successfully converted into benzo[b]phenanthridine-7,12-dione through treatment with aqueous ammonia, followed by oxidative cyclization using MnO2.

How To Reach Intense Luminescence for Compounds Capable of Excited-State Intramolecular Proton Transfer?

Photoinduced intramolecular direct arylation allows structurally unique compounds containing phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridine and imidazo[1,2-f]phenanthridine skeletons, which mediate excited-state intramolecular proton transfer (ESIPT), to be efficiently synthesized. The developed polycyclic aromatics demonstrate that the combination of five-membered ring structures with a rigid arrangement between a proton donor and a proton acceptor provides a means for attaining large fluorescence quantum yields, exceeding 0.5, even in protic solvents. Steady-state and time-resolved UV/Vis spectroscopy reveals that, upon photoexcitation, the prepared protic heteroaromatics undergo ESIPT, converting them efficiently into their excited-state keto tautomers, which have lifetimes ranging from about 5 to 10 ns. The rigidity of their structures, which suppresses nonradiative decay pathways, is believed to be the underlying reason for the nanosecond lifetimes of these singlet excited states and the observed high fluorescence quantum yields. Hydrogen bonding with protic solvents does not interfere with the excited-state dynamics and, as a result, there is no difference between the occurrences of ESIPT processes in MeOH versus cyclohexane. Acidic media has a more dramatic effect on suppressing ESIPT by protonating the proton acceptor. As a result, in the presence of an acid, a larger proportion of the fluorescence of ESIPT-capable compounds originates from their enol excited states.

ChemInform Abstract: 2‐Oxo‐Driven N2 Elimination Induced Decarbonylative Cyclization Reaction in Benzotriazoles to 6‐Aminophenanthridines.

AbstractA variety of functional groups can be introduced in the phenanthridine skeleton following the 3‐component strategy shown.

ChemInform Abstract: Phosphine‐Catalyzed [4 + 3] Cycloaddition Reaction of Aromatic Azomethine Imines with Allenoates.

AbstractAn efficient access to a variety of highly valuable diazepine derivatives annulated with an isoquinoline, quinoline, or phenanthridine skeleton is developed.

Expeditious Approach to Pyrrolophenanthridones, Phenanthridines, and Benzo[c]phenanthridines via Organocatalytic Direct Biaryl-Coupling Promoted by Potassium tert-Butoxide

A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KO(t)Bu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).

Total Synthesis of Jadomycins B, S, T, and ILEVS1080

Sweetening up jadomycin A: The first total synthesis of jadomycins B, S, T, and ILEVS1080 has been achieved, featuring construction of the unique 8H-benz[b]oxazolo[3,3-f]phenanthridine skeleton by biomimetic condensation of a quinone aldehyde with amino acid sodium salts and elaboration of the glycosides by Mitsunobu condensation (see figure).

ChemInform Abstract: Synthesis of 8‐Aryl‐Substituted Benzo[a]phenanthridine Derivatives by Consecutive Three‐Component Tandem Reaction and 6‐endo Carbocyclization.

AbstractThe ICl‐promoted reaction of quinolines (I) introduces a 7‐iodo substituent into the benzo[a]phenanthridine skeleton and allows further functionalization by Pd‐catalyzed coupling reactions.

Ungeremine and Its Hemisynthesized Analogues as Bactericides against Flavobacterium columnare

The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.

Total Synthesis of (+)-trans-Dihydronarciclasine Utilizing Asymmetric Conjugate Addition

A highly efficient short-step construction of the common phenanthridine skeleton of pancratistatin-class alkaloids was accomplished in enantiomerically pure form using chiral ligand-controlled asymmetric conjugate addition. The utility of the intermediate was demonstrated by the total synthesis of (+)-trans-dihydronarciclasine with mild oxidation from an amine to an amide as a key step.

ベンゾ［c］フェナンスリジン·アルカロイドおよび関連化合物の合成研究

Benzo[c]phenanthridine alkaloids are distributed in Papaveraceous and Rutaceous plants and classified into two categories of fully aromatized bases and partially hydrogenated bases(B/C-cis-11-hydroxyhexahydrobenzo[c]phenanthridine skeleton). They have long history, in which the first isolation of chelidonine, a partially hydrogenated base, from Papaveraceous plant, was reported in 1839. Over a century later nitidine and fagaronine, O4-type fully aromatized bases isolated from Rutaeceous plant, attracted much attention because of their antitumor activity. At present, a variety of pharmacological effects are recognized in natural and unnatural species. We, about forty years ago, started synthetic studies on fully aromatized bases focusing on structure-activity relationship of antitumor activity and succeeded in establishing widely-applicable synthetic methods. Recently the enantioselective synthesis of chelidonine was completed. Thus, in this review, we present our chemical history for the synthesis of benzo[c]phenanthridine bases.

Synthesis of Phenanthridinones and Phenanthridine Derivatives through Palladium-catalyzed Oxidative C–H Coupling of Benzanilides

Abstract A palladium-catalyzed oxidative C–H coupling reaction of benzanilides using molecular oxygen as the oxidant furnishes phenanthridinones. The palladium-catalyzed reaction in combination with simple derivatization provides an efficient access to a phenanthridine skeleton starting from readily available benzoic acids and anilines.

Enantioselective synthesis of chelidonine, a B/C- cis-11-hydroxyhexahydrobenzo[ c]phenanthridine alkaloid

Both enantiomers of chelidonine, a B/C- cis-11-hydroxyhexahydrobenzo[ c]phenanthridine alkaloid, were synthesized by manipulation of the B/C-dehydro ring juncture of benzo[ c]phenanthridine skeleton using Sharpless asymmetric dihydroxylation and stereospecific catalytic hydrogenation after introduction of oxygen functions on the C ring as key reaction steps for the construction of stereogenic centers.

Fused heterocyclic amido compounds as anti-hepatitis C virus agents

We identified a fused heteroaromatic amido structure based on the phenanthridine skeleton as a superior scaffold for candidate drugs with potent anti-HCV activity. Among the compounds synthesized, a phenanthridine analogue with a 1,3-dioxolyl group ( 24) possessed the most potent anti-HCV activity (EC 50 value: 50 nM), with acceptable cytotoxicity. The structural development and structure–activity relationships of these compounds are described.

Synthetic studies on jadomycins: synthesis of dimethyljadomycin A

Dimethyljadomycin A was synthesized as the first example for the construction of 8H-benzo[b]oxazolo[3,2-f]phenanthridine skeleton.

Total synthesis of 12-methoxydihydrochelerythrine and anti-tumour activity of its quaternary base: toward an efficient synthetic route for 12-alkoxybenzo[c]phenanthridine bases via naphthoquinone monooxime from 2-benzofuranyl-1-tetralone derivative.

A concise total synthesis of 12-methoxydihydrochelerythrine (6), isolated from Bocconia integrifolia, is described. The synthesis features an efficient route to a 12-alkoxybenzo[c]phenanthridine skeleton via naphthoquinone monooxime 11 as a key compound. Starting from 7-methoxy-2-methylbenzo[b]furan (9), 3-aryl-1-tetralone 10 was synthesised, followed by aromatisation to 3-aryl-1-naphthol 17. After oxidative cleavage of the furan ring, basic nitrosation of naphthol 22 gave the naphthoquinone 11. The benzo[c]phenanthridine skeleton was formed by reductive cyclisation of 11. Deoxygenation of the lactam moiety in 23 afforded nor-base 32 and methylation of 32 under reductive conditions gave the target dihydro base 6 (23 steps from benzofuran 9 in 10% overall yield). The corresponding quaternary base 7 showed moderate anti-tumour activity against cancer cell lines; on NCI-H460: IC50 4.5 microM and on MDA-MB-231: IC50 1.2 microM. Introduction of a methoxy group into the 12-position of the benzo[c]phenanthridine skeleton could cause enhanced activity against MDA-MB-231 by comparison of 7 with chelerythrine (35) (IC50 5.3 microM).

ChemInform Abstract: A Novel Synthesis of Benzo[c]phenanthridine Skeleton and Biological Evaluation of Isoquinoline Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A novel synthesis of benzo[c]phenanthridine skeleton and biological evaluation of isoquinoline derivatives.

Benzo[c]phenanthridine skeleton was synthesized from easily available starting N-methyl-o-toluamide 2 and o-methylbenzonitrile 5 in 7 steps. Radical cyclization of styrene 10 afforded 6,11-dimethyl-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one 13. Most 3-arylisoquinolines have displayed strong activities against human tumor cell lines. Especially, indenoisoquinolinone 13 exhibited excellent cytotoxicity (IC50 = 0.002 microgram/ml; HCT 15).

1,3‐Dipolar Cycloadditions of Phenanthridinium‐Based Azomethine Ylides

AbstractAzomethine ylides generated from 5‐(alkoxycarbonylmethyl)phenanthridinium cations were studied in 1,3‐dipolar cycloadditions with dimethyl maleate and dimethyl fumarate as dipolarophiles. The cycloadducts with the pyrrolidino[1,2‐f]phenanthridine skeleton easily underwent dehydrogenation. The structure of products was determined by X‐ray, NMR and MS.

A convenient synthesis of N-methyl-3-(2-ethenylphenyl)-1(2 H)-isoquinolones, key models for the elaboration of the benzo[ c]phenanthridinone and phenanthridine skeletons

A variety of N-methyl-3-(2-ethenylphenyl)-1(2 H)-isoquinolones 1a–e have been prepared by base-induced intramolecular cyclization of N-(2-ethenylbenzoyl)- N,2-dimethylbenzamide derivatives 2a–e. The concomitant formation of the fused dihydro benzo[ c]phenanthridinones 7a–e was also observed during this process.