Phenanthridine Ring Research Articles

Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides.

Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter's crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M-1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals.

Selective formation of a phenathridine derivative by photodegradation of azilsartan

Photodegradation of azilsartan produces a phenanthridine derivative, with its molecular structure determined by 1H and 13C NMR spectroscopy. This structure is confirmed by single-crystal X-ray diffraction and alternative synthesis. The phenanthridine ring formation is explained through the ring closure of an imidoylnitrene intermediate produced by decarboxylation of the 5-oxo-1,2,4-oxadiazole ring (oxadiazolone).

DNA Intercalation Facilitates Efficient DNA-Targeted Covalent Binding of Phenanthriplatin.

Phenanthriplatin, a monofunctional anticancer agent derived from cisplatin, shows significantly more rapid DNA covalent-binding activity compared to its parent complex. To understand the underlying molecular mechanism, we used single-molecule studies with optical tweezers to probe the kinetics of DNA-phenanthriplatin binding as well as DNA binding to several control complexes. The time-dependent extensions of single λ-DNA molecules were monitored at constant applied forces and compound concentrations, followed by rinsing with a compound-free solution. DNA-phenanthriplatin association consisted of fast and reversible DNA lengthening with time constant τ ≈ 10 s, followed by slow and irreversible DNA elongation that reached equilibrium in ∼30 min. In contrast, only reversible fast DNA elongation occured for its stereoisomer trans-phenanthriplatin, suggesting that the distinct two-rate kinetics of phenanthriplatin is sensitive to the geometric conformation of the complex. Furthermore, no DNA unwinding was observed for pyriplatin, in which the phenanthridine ligand of phenanthriplatin is replaced by the smaller pyridine molecule, indicating that the size of the aromatic group is responsible for the rapid DNA elongation. These findings suggest that the mechanism of binding of phenanthriplatin to DNA involves rapid, partial intercalation of the phenanthridine ring followed by slower substitution of the adjacent chloride ligand by, most likely, the N7 atom of a purine base. The cis isomer affords the proper stereochemistry at the metal center to facilitate essentially irreversible DNA covalent binding, a geometric advantage not afforded by trans-phenanthriplatin. This study demonstrates that reversible DNA intercalation provides a robust transition state that is efficiently converted to an irreversible DNA-Pt bound state.

A mild acid-free one-pot reaction for synthesis of new phenanthridine dyes

A series of new phenylphenanthridin dyes have been synthesized in the yields of 52–75% by a mild strategy in one-pot reaction. This is the first successful attempt to perform efficient soft acid-free reaction for phenanthridine ring construction. A large substrate scope was well demonstrated.

Recent Progress Towards the Total Synthesis and Biological Studies of Calothrixin A and B

Calothrixin A and B are pentacyclic alkaloids isolated from Calothrix Cyanobacteria with unique structural features containing indolo[3,2-j]phenanthridine ring system. These alkaloids possess various biological activities including growth inhibitory effects on a chloroquine-resistant strain of the malarial parasite Plasmodium falciparum and activity against human cancer cells. In this review, various synthetic approaches developed so far for calothrixin A & B and their bioactivities are described. Keywords: Alkaloid, biogenesis, calothrixin, cyanobacteria, natural product, phenanthridine.

ChemInform Abstract: Palladium‐Catalyzed Intramolecular C—H Bond Functionalization of Trifluoroacetimidoyl Chloride Derivatives: Synthesis of 6‐Trifluoromethyl‐phenanthridines.

Abstract Highly efficient approaches to obtain 6-trifluoromethyl-phenanthridine derivatives have been realized through the palladium-catalyzed intramolecular C–H bond functionalization of trifluoroacetimidoyl chlorides. The reaction allows the direct formation of CSp2–CSp2 bonds via C–H bond functionalization and rapid access to phenanthridine ring systems in moderate to high yields with good functional group tolerance.

Palladium-catalyzed intramolecular C−H bond functionalization of trifluoroacetimidoyl chloride derivatives: Synthesis of 6-trifluoromethyl-phenanthridines

Highly efficient approaches to obtain 6-trifluoromethyl-phenanthridine derivatives have been realized through the palladium-catalyzed intramolecular C–H bond functionalization of trifluoroacetimidoyl chlorides. The reaction allows the direct formation of CSp2–CSp2 bonds via C–H bond functionalization and rapid access to phenanthridine ring systems in moderate to high yields with good functional group tolerance.

Synthesis of 6‐Phenanthridinephosphonates via a Radical Phosphonation and Cyclization Process Mediated by Manganese(III) Acetate

Abstract6‐Phenanthridinephosphonates have interesting biological activities and potential pharmaceutical applications. However, methods for preparing these compounds are very limited. In this report, dialkyl 6‐phenanthridinephosphonates were synthesized through Mn(OAc)3‐mediated radical phosphonation of 2‐isocyanobiaryls in good to excellent yields under relatively mild reaction conditions. As one of its notable features, the radical process allows the direct formation of a PC bond and the construction of a phenanthridine ring in one reaction.

ChemInform Abstract: PhI(OAc)2‐Mediated Synthesis of 6‐(Trifluoromethyl)phenanthridines by Oxidative Cyclization of 2‐Isocyanobiphenyls with CF3SiMe3 under Metal‐Free Conditions.

A mild and efficient method for the synthesis of 6-(trifluoromethyl)phenanthridines through oxidative cyclization of 2-isocyanobiphenyls with CF3SiMe3 under metal-free conditions was developed. The reaction allows the direct formation of C–CF3 bonds and rapid access to phenanthridine ring systems in one catalytic cycle.

Synthesis and evaluation of anti-tubercular activity of 6-(4-substitutedpiperazin-1-yl) phenanthridine analogues

A series of seventeen new 6-(4-substitutedpiperazin-1-yl)phenanthridine derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv by Microplate Alamar Blue Assay and most active compounds were tested for cytotoxicity studies against mouse macrophage cell lines (RAW264.7). Among the tested compounds, ten compounds exhibited significant activity against the growth of M. tuberculosis (MIC ranging from 1.56 to 6.25 μg/mL). In particular, compounds 5e, 5j and 5k displayed excellent activity against the growth of M. tuberculosis (MIC 1.56 μg/mL). The selectivity index values were found to be >25, indicating compounds likeliness in drug development for tuberculosis. The structure of 5k is substantiated by X-ray crystallographic study. Structure–activity correlation indicates the importance of substituent at 4th position of piperazinyl phenanthridine ring.

PhI(OAc)2-Mediated Synthesis of 6-(Trifluoromethyl)phenanthridines by Oxidative Cyclization of 2-Isocyanobiphenyls with CF3SiMe3 under Metal-Free Conditions

A mild and efficient method for the synthesis of 6-(trifluoromethyl)phenanthridines through oxidative cyclization of 2-isocyanobiphenyls with CF3SiMe3 under metal-free conditions was developed. The reaction allows the direct formation of C-CF3 bonds and rapid access to phenanthridine ring systems in one catalytic cycle.

Synthesis of Benzo[c]phenanthridine Alkaloids by Pd(OAc)2‐Induced Direct Aromatic Carbonylation

AbstractThe Pd(OAc)2‐induced carbonylation of alkoxy‐substituted 1‐amino‐2‐phenyltetralins and 1‐amino‐2‐phenylnaphthalenes was examined to provide the benzo[c]phenanthridine ring system. The carbonylation of substrates containing methylenedioxy groups gave oxysanguinarine and oxyavicine. The tetramethoxy derivatives gave O‐methyloxyfagaronine. The substrate with a benzyloxy group afforded a known synthetic precursor to the antileukemic alkaloid, fagaronine.

A new entry to the phenanthridine ring system

A new synthesis of phenanthridine derivatives having three-point diversity has been developed based on the sequential application of three-atom economic processes viz. aza-Claisen rearrangement, ring-closing enyne metathesis and Diels–Alder reaction as key steps. An unexpected isomerisation was observed during aza-Claisen rearrangement of N-allylanilines which may open up new opportunities in heterocyclic synthesis.

ChemInform Abstract: A Very Short Route to Fully Aromatic 2,3,8,9- and 2,3,8,9,12- Oxygenated Benzo(c)phenanthridines.

Cyclisation of suitably substituted 2-benzylamino-2-phenylacetonitries proceeds by rearrangement, in sulphuric acid or anhydrous hydrogen fluoride, to give 3-aryl-1,2-dihydroisoquinolinones possessing all but two carbons of the benzo[c]phenanthridine ring system. These two carbon atoms are introduced in high yield by means of a modified Reformatski reaction and the resulting ester is cyclised in sulphuric acid, with concomitant dehydration and oxidation, to give the fully aromatic four-ring system in only four steps.

Multicomponent Approach for the Synthesis of Phenanthridine and Acridine Ring Systems via the Coupling of Fischer Carbene Complexes with Hetero­aromatic o-Alkynyl Carbonyl Derivatives

A one-pot multicomponent synthesis of phenanthridine and acridine derivatives is described. This method includes the in situ generation of furo[3,4-c]isoquinoline and furo[3,4-b]quinoline intermediates by the coupling of heteroaromatic o-alkynyl carbonyl derivatives with Fischer carbene complexes and subsequent trapping of these intermediates by suitable dienophiles.

ChemInform Abstract: Synthesis of NK109, an Anticancer Benzo[c]phenanthridine Alkaloid.

A total synthesis of NK109 (7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridinium hydrogensulfate dihydrate), an anticancer benzo[c]phenanthridine alkaloid, is reported. The primary structure of this compound was erroneously communicated in 1973 as fagaridine (from Fagara xanthoxyloides) which is the 8-hydroxy regioisomer. NK109 has not yet been isolated from a natural source and therefore can only be obtained by synthesis. To study a wide variety of analogues, we decided to use a synthetic route via substituted benzylamine 5, which was obtained from the appropriate benzaldehyde and naphthylamine units. The benzo[c]phenanthridine ring was constructed by radical cyclization with tri-n-octyltin hydride and 2,2‘-azobis(2-methylbutyronitrile), followed by oxidative aromatization with MnO2. The resulting benzo[c]phenanthridine 6 was successfully methylated with methyl 2-nitrobenzenesulfonate. After deprotection of the benzyl group and subsequent hydration, NK109 was obtained. All reactions we...

12-Ethoxy-2,3,8,9-tetramethoxybenzo[c]phenanthridine dichloromethane solvate

The title compound, C23H23NO5·CH2Cl2, was obtained via the alkyl­ation of the 12-hydr­oxy-2,3,8,9-tetra­methoxy­benzo[c]phenanthridine salt. The benzo[c]phenanthridine ring system is essentially planar, with a mean out-of-plane deviation of 0.026 Å. A dicloromethane mol­ecule of solvation is present and located between the sheets of phenanthridine mol­ecules, preventing any significant inter­molecular hydrogen-bonding or π–π inter­actions.

ChemInform Abstract: Tandem Generation and Trapping of Furo[3,4‐c]isoquinoline Intermediates Leading to the Synthesis of Phenanthridine Ring Systems.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Tandem Generation and Trapping of Furo[3,4-c]isoquinoline Intermediates Leading to the Synthesis of Phenanthridine Ring Systems

One pot three component coupling of 3-alkynyl-4-isoquinoline carbonyl derivatives with Fischer carbene complexes and dienophiles leading to the synthesis of phenanthridine ring system has been investigated. This reaction involves the generation of furo[3,4-c]isoquinolines as transient intermediates, which undergo [4+2] cycloaddition with a dienophile in an inter/intramolecular fashion. In fact, this is the first report of the work on furo[3,4-c]isoquinoline intermediates. Keywords: Azaisobenzofuran, carbene complexes, chromium, Diels-Alder reaction, phenanthridine

Dichloridobis(phenanthridine-κN)zinc(II)

In the mol­ecule of the title compound, [ZnCl2(C13H9N)2], the ZnII atom is four-coordinated in a distorted tetra­hedral configuration by two N atoms from two phenanthridine ligands and by two terminal Cl atoms. The dihedral angle between the planes of the phenanthridine ring systems is 69.92 (3)°. An intra­molecular C—H⋯Cl inter­action results in the formation of a planar five-membered ring, which is oriented at a dihedral angle of 8.32 (3)° with respect to the adjacent phenanthridine ring system. In the crystal structure, π–π contacts between the phenanthridine systems [centroid–centroid distances = 3.839 (2), 3.617 (1) and 3.682 (1) Å] may stabilize the structure. Two weak C—H⋯π inter­actions are also found.