Phenanthridines substitution

Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines substituted at the 11- and 12-positions as novel topoisomerase l-targeting antitumor agents... 

Azonia substitution at a naphthalene bridgehead position gives the quinolizinium ion (16). Oxonia substitution, elsewhere, forms the 1- and 2-benzopyrylium ions (17) and (18). The two most well-known monoaza systems with three aromatie fused rings are aeridine (19), derived structurally from anthraeene, and phenanthridine (20), an azaphenanthrene. The better-known diaza systems inelude phenazine (21) and 1,10-phenanthroline (22), while systems with three linearly fused pyridine rings are ealled anthyridines, e.g. the 1,9,10-isomer (23). 

Demethylvasconine (85) (9-methoxy-5-methyl-phenanthridin-8-olate) presented in Scheme 31 was found in Crinum kirkii (95P1291) (Amaryllidaceae). Although published as cation, no information about the anion of this alkaloid is given. Its relationship to other alkaloids of this class, however, makes a betainic structure more than likely and this is confirmed by a comparison of the NMR data of 85 with the cationic and betainic alkaloids presented in Table III. This betaine is isoconjugate with the 2-methylphenanthrene anion and thus defined the alkaloid as a member of class 1 (odd alternant hydrocarbon anions). Whereas substitution of the isoconjugate phenanthridinium moiety at the 1-position with an anionic fragment results in zwitterions (cf. Section III.D), the phenanthridinium-2-olate is a mesomeric betaine. 

Thus, the phenanthridine-fused benzaldehyde triazinylhydrazone 229 was cyclized by using thionyl chloride to the phenyl substituted pentacyclic product 230 <1998NN1385>. The corresponding methyl-substituted fused system... 

Quinoline, isoquinoline, and phenanthridine resemble pyridine in reacting comparably, and diketene may he substituted for ketene. 

Similar types of nucleophilic substitutions have also been carried out when PIFA is activated by two equivalents of Lewis acids such as trimethylsilyl triflu-oromethanesulfonate (TMSOTf) and BF3 Et20 or heteropolyacid in standard solvents such as CH2C12 and MeCN. These reactions were applied to intramolecular reactions by the same authors leading to biaryls (49) [54-57], quinone imine derivatives (50) [58], and dihydrobenzothiophens (51) [59], which are important structures of bioactive natural products [Eqs. (7)-(9)]. Dominguez and co-workers have expanded the above biaryl coupling reaction to the syntheses of benzo[c]phenanthridine system (52) [60] and heterobiaryl compounds (53) [61] [Eqs. (10,11)]. 

One of the most important design changes in the evolution of this type of sensor was to produce complexes stable in aqueous media. The cyclen-based ligands and their stable Eu(III) and Tb(III) complexes, 44-46, represent examples of sensors developed by Parker et al. for pH, p02, halide and hydroxide ion sensing, [148-150]. The ligand used was based on cyclen substituted in one of the four positions with phenanthridine as the antenna and receptor. The other three positions were substituted with various pendant... 

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

Although phenanthridine was discovered in the late nineteenth century1, 2 neither the parent base nor its derivatives attracted attention until useful therapeutic activity was established in certain quaternary phenanthridinium compounds.3 A substantial number of substituted phenanthridines (and many phenanthridinium salts) have now been described and lists of compounds appearing in the literature from 1884 until 1955 are available.4, 6 Phenanthridines have attracted surprisingly little systematic attention, although the system is of considerable theoretical interest and, with its nine nonequivalent carbon atoms, may be expected to provide a rigorous test of molecular orbital reactivity correlations. Naturally occurring derivatives include several Amaryllidaceae and Papaveraceae alkaloids, notably, lycorine, haemanthamine, and chelidonine the chemistry of the phenanthridine alkaloids has been reviewed.6... 

The products are described,192 apparently incorrectly, as 4-substituted rather than 3-substituted phenanthridines. 

Calculated reactivity indices are at one with qualitative electronic theory in accounting for ready nucleophilic attack at C-6 in the phenanthridine molecule. However, the limited data available on positional reactivities in electrophilic substitutions is not accounted for satisfactorily by any of the available treatments (see later) and it has been pointed out that the simple Hiickel treatment used by some authors,223, 220 is generally inapplicable in heteroaromatic systems.228... 

The introduction of a methyl group at C-6 of phenanthridine is relatively more rate depressing than a similar substitution at C-2 in... 

Previous reviewers have commented4, 5 on the lack of information concerning the substitution reactions of phenanthridine. Although some progress has been made in this field, systematic studies are still much needed. 

Although, predictably, C-6 of the phenanthridine ring is susceptible to nucleophilic attack, until recently only qualitative reactivity data were available. New examples of both direct substitutions (hydride ion extrusion) and nucleophilic replacements, notably of halogen atoms, have been reported since the last review.6... 

Aminative replacement in compounds other than those bearing halogen atoms are uncommon, but 6-aminophenanthridine is easily prepared by heating 6-phenoxyphenanthridine with urea296 and 6-anilinophenanthridine has been obtained by the action of aniline on the 6-phenoxy compound.268 The formation of 6-anilinophenanthridine from phenanthridine iV-oxide and phenyl isocyanate probably proceeds via an initial 1,3-dipolar addition, followed by nucleophilic substitution and decarboxylation (Scheme 4).309... 

Volume 13 of this serial publication comprises six chapters of which four deal with general accounts of compound classes 1-azirines (F. W. Fowler), phenanthridines (B. R. T. Keene and P. Tissington), tri-thiapentalenes (N. Lozac h), and heterocyclic ferrocenes (F. D. Popp and E. B. Moynahan). The other two chapters are concerned with particular aspects of the chemistry of groups of heterocyeles the tautomerism of purines (B. Pullman and A. Pullman) and quantitative aspects of the electrophilic substitution reactions of five-membered rings (G. Marino). 

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