Angular Isomer Research Articles

Synthesis and Antifungal Activity of Chromones and Benzoxepines from the Leaves of Ptaeroxylon obliquum

This study reports the first total synthesis of the bioactive oxepinochromones 12-O-acetyleranthin (8) (angular isomer) and 12-O-acetylptaeroxylinol (9) (linear isomer). The antifungal activity of these compounds and their derivatives was determined against Candida albicans and Cryptococcus neoformans. Most compounds had good selectivity between the two fungi and showed moderate to good activity. 12-O-Acetyleranthin (8) had the highest activity against C. albicans, with an MIC value of 9.9 μM, while 12-O-acetylptaeroxylinol (9), the compound present in Ptaeroxylon obliquum, had the highest activity against C. neoformans, with an MIC value of 4.9 μM.

Computational and Experimental Study on Molecular Structure of Benzo[g]pyrimido[4,5-b]quinoline Derivatives: Preference of Linear over the Angular Isomer

A series of 5-aryl-2-methylthio-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-4,6,11(3H)-trione was synthesized through an environmental friendly multicomponent methodology and characterized with FT-IR (Fourier Transform infrared spectroscopy), 1H NMR (Nuclear Magnetic Resonance ), 13C NMR and GC-MS (gas chromatography-mass spectrometry). The 5-(4-methoxyphenyl)-2-methylthio-5,12-dihydrobenzo[g]pyrimido[4,5-b]quinoline-4,6,11(3H)-trione 4c compound was characterized by X-ray single crystal diffraction. The geometry of 4c has been fully optimized using DFT (Density functional theory), B3LYP functional and 6-31G(d,p) basis set, thus establishing the ground state energy and thermodynamic features for the mentioned compound, which are in accordance with the experimental data and the crystal structure. The experimental results reveal a strong preference for the regioselective formation of 4c linear four fused rings over the angular four fused and suggest a possible kinetic control in product formation.

Synthesis of Benzobis[1,3]oxathiins

AbstractTwo different synthetic concepts led to the formation of 17, 19, and 29, the first structural isomeric benzobis[1,3]oxathiins. Hetero‐DielsAlder reactions of diethyl mesoxylate 14 and the open valence isomers of the benzobisthietes 12 and 18 yielded the linear benzobis[1,3]oxathiin 17 and its angular isomer 22, respectively. The isomeric angular system 29 could be obtained by a twofold O,S‐acetalization reaction of the dihydroxydisulfanyl compound 27 and acetone (28).

Influence of the -CH2X substituent on the regioselectivity of intramolecular meta-photocycloaddition reactions.

In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin by an intramolecular meta-photocycloaddition, it was found that the regioselectivity of the reaction depends strongly on the substituent -CH2X in the ortho-position to the tether. Electropositive groups X (X = H, Me, TMS, TES) gave preferentially the linear isomer (regioisomeric ratio = 87/13 to >95/5), whereas electronegative substituents (X = OH, OAc, F) showed a clear preference for the angular isomer (regioisomeric ratio = 75/25 to >95/5). The silylated and fluorinated products were obtained as single isomers in moderate yield.

Symmetrical Bisbenzimidazoles with Benzenediyl Spacer: The Role of the Shape of the Ligand on the Stabilization and Structural Alterations in Telomeric G-Quadruplex DNA and Telomerase Inhibition

The extremities of chromosomes end in a G-rich single-stranded overhang that has been implicated in the onset of the replicate senescence. The repeated sequence forming a G-overhang is able to adopt a four-stranded DNA structure called G-quadruplex, which is a poor substrate for the enzyme telomerase. Small molecule based ligands that selectively stabilize the telomeric G-quadruplex DNA, induce telomere shortening eventually leading to cell death. Herein, we have investigated the G-quadruplex DNA interaction with two isomeric bisbenzimidazole-based compounds that differ in terms of shape (V-shaped angular vs linear). While the linear isomer induced some stabilization of the intramolecular G-quadruplex structure generated in the presence of Na(+), the other, having V-shaped central planar core, caused a dramatic structural alteration of the latter, above a threshold concentration. This transition was evident from the pronounced changes observed in the circular dichroism spectra and from the gel mobility shift assay involving the G-quadruplex DNA. Notably, this angular isomer could also induce the G-quadruplex formation in the absence of any added cation. The ligand-quadruplex complexes were investigated by computational molecular modeling, providing further information on structure-activity relationships. Finally, TRAP (telomerase repeat amplification protocol) experiments demonstrated that the angular isomer is selective toward the inhibition of telomerase activity.

Heterocyclic Systems Containing Bridgehead Nitrogen Atom: Synthesis and Bioactivity of Thiazolo[3′,2′:2,3]‐as‐triazino[5,6‐b]indoles and Isomeric Thiazolo[2′,3′:3,4]‐as‐triazino[5,6‐b]indoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Convenient Preparation of 2-(2-Arylidene)- and 2-(2-Polyhydroxyalkylidene)hydrazono-4-imidazolidinones with Various Heterocyclic Side Chain Substituents at Position 5 as Potential Antiviral and Antitumor Agents

A variety of novel 5-[( Z )-arylidene]-2-[(2-( E )-arylidene)hydrazono]-4-imidazolidinones 1a-c to 4a , b and 5-[( Z )-arylidene]-2-[(2-( E )-polyhydroxyalkylidene)hydrazono]-4-imidazolidinones 5a-c to 7a-c were prepared from the reaction of 5-[( Z )-arylidene]-2-methylmercaptohydantoins 8a-c with 2-( E )-arylidene hydrazones 13a-d and/or 2-( E )-monosaccharides hydrazones 16a-c . The linear structure, and not that of the angular isomer, has been selected for the products. This structure has been confirmed from a model study of the condensation of 5-[( Z )-2-thienylidene]-2-hydrazono-4-imidazolidinone 9a with benzaldehyde and D -galactose, respectively. The acetylation and benzoylation reactions of compounds 1-7 have been studied. All the new compounds were tested for their potential antiviral and antitumor activities.

The X-ray crystal structure of linear [3]phenylene

The X-ray structure of the parent linear [3]phenylene (benzo[3,4]cyclobuta[1,2- b]biphenylene) has been obtained and is compared with those of its angular isomer and model compounds. The terminal rings reveal a relatively large degree of bond alternation while the center distorts to a cyclic bisallyl frame.

Acyclo C-Nucleoside Analogs. Regioselective Annellation of a Triazole Ring to 5-Methyl-1,2,4-Triazino[5,6-b]Indole and Formation of Certain 3-Poly Hydroxyalkyl Derivatives

ABSTRACT Cyclodehydrogenation of the ethylidene derivative of (5-methyl-1,2,4-triazino[5,6-b]indol-3-yl)hydrazine (1) gave the angular isomer, 1,10-dimethyl-1,2,4-triazolo[3′,4′:3,4][1,2,4]triazino[5,6-b]indole (4). The linear isomer, 3,10-dimethyl-1,2,4-triazolo[4′,3′:2,3][1,2,4]triazino[5,6-b]indole (7) could be prepared regioselectively by the cyclodehydration of the acetyl derivative of 1. The cyclodehydrogenation was extended to the monosaccharide derivatives of 1. The role of the N-methyl group on the site of annellation has been discussed.

Synthesis of Acyclo C-Nucleosides OF Phenanthro[9,10-e][1,2,4]Triazino[3,4-c]-[1,2,4] Triazoles, and Their Precursors

ABSTRACT Reaction of 3-hydrazinophenanthro[9,10-e][1,2,4]triazine (1) with aliphatic and aromatic aldehydes as well as monosaccharides gave the corresponding hydrazones 2a-g. The D-glucose analogue exists in the cyclic pyranosyl structure 5. Acetylation and partial acetylation of the sugar hydrazones were carried out. Cyclization of a number of hydrazones including the partially acetylated sugar hydrazones by thionyl chloride gave regioselectively the respective angular isomer 1-substituted phenanthro[9,10-e][1,2,4]triazino[3,4-c][1,2,4]triazoles 16i-I, and not the linear isomer. The cyclization of 1 with acetic acid, however, gave regioselectively the linear isomer 19. The structural assignments were based on a model study whereby the angular 16a was found to be different from the linear isomer 19a obtained by the condensation of 4,5-diamino-3-methyl-1,2,4-triazole with 9,10-phenanthraquinone. Periodate oxidation of 2d gave 20 whose reaction with 1 gave 21.

Furocoumarins and Other Secondary Metabolites from Psoralea canescens

The furocoumarin and other chemical constituents from Psoralea canescens, a perennial legume from North America, were investigated. Two furocoumarins, psoralen and its angular isomer, angelicin, and two other major components (propenoic acid derivatives) were isolated and identified by spectroscopic methods. P. canescens contains furocoumarins in both free and bound forms. The psoralen/angelicin ratios show that psoralen is predominant in all plant organs. Furocoumarins were shown to accumulate mainly in the roots, smaller amounts being present in the flowers and immature fruits. Considering the good dry matter production of Psoralea canescens, this species appears to be a valuable natural source of furocoumarins.

A Theoretical Study on Intramolecular Cyclization of Azidobenzotriazine to Tetrazolobenzotriazines

Abstract The cyclization equilibrium of 3-azidobenzo[l,2,4]triazine (1 a) with tetrazolo[5,1-b]benzo[1,2,4] triazine (linear isomer, 1 b) and tetrazolo[5,1-c]benzo[1,2,4]triazine (angular isomer, 1 c) is investigated computationally using the molecular orbital MNDO-SCF method. The results suggest that the higher reactivity of atom N(4) with respect to N(2) towards the cyclization is due to: (i) The negative charge density upon N(4) is 1.3 time larger than that upon N(2); (ii) In the highest occupied molecular orbital (HOMO) the coefficient at N(4) is 2.4 times larger than that at N(2); (iii) The heat of reaction to (1 c) and (1 b) are calculated to be -74.9 and -14.8 kJ mol -1 , respectively; (iv) The thermodynamic stabilization of the angular isomer (1 c) is 60.1 kJ mol-1 larger than that of the linear isomer (1 b), and (v) The potential barrier heights calculated for the cyclization favour the angular product. From these considerations and the perturbation theory, the calculated yield of the cyclization reaction is 70.8±0.1% of 1 c, which is in good agreement with the experimental yield 64%.

Concise Syntheses of the Novel 1H-Pyrrolo[3,2-g]quinazoline Ring System and its [2,3-f] Angular Isomer

Concise Syntheses of the Novel 1<i>H</i>-Pyrrolo[3,2-<i>g</i>]quinazoline Ring System and its [2,3-<i>f</i>] Angular Isomer

Development of an enzyme immunoassay to detect and quantify psoralen and bergapten in plants

AbstractA competitive enzyme immunoassay has been developed in order to quantify furanocoumarins. 5‐Hydroxypsoralen was modified and linked to bovine serum albumin to obtain an antigenic response. The rabbit serum that was collected was highly specific to 5‐methoxypsoralen and psoralen but did not recognize angelicin (a psoralen angular isomer), 8‐methoxypsoralen or 5,8‐dimethoxypsoralen, coumarin and related molecules. The detection limit was about 5 ng/mL for 5‐methoxypsoralen and 30 ng/mL for psoralen. The test was applied to plants that contain furanocoumarins i.e. species of Psoralea. The correlation with a classical high‐pressure liquid chromatographic method was satisfactory with both dry and fresh matter. With reference to the extraction method used with the plant material, the detection limit in the plant samples was about 15 μg/g for the dry matter and 20 μg/g for the fresh matter. This technique is a useful tool to detect and quantify psoralen and 5‐methoxypsoralen in plant samples.

Regioisomeric Formation of Acenaphtho[1,2-e][1,2,4]triazolo[3,4-c][1,2,4]triazines and Their Acyclic C-Nucleoside Analogues

Abstract The oxidative cyclization of the ethylidene derivative of 3-hydrazinoacenaphtho[1,2-e][1,2,4]triazine (2) gave regioselectively the angular isomer 1-methylacenaphtho[1,2-e][1,2,4]triazolo[3,4-c][1,2,4]triazine (5). Its linear isomer 10-methylacenaphtho[1,2-e][1,2,4]triazolo[4,3-b][1,2,4]triazine (4) was synthesized by the condensation of acenaphthenequinone (6) with 3,4-diamino-5-methyl-4H-1,2,4-triazole. Condensation of 2 with a number of monosaccharides afforded the respective hydrazones 9 whose oxidative cyclization gave the corresponding 1-(polyhydroxyalkyl)acenaphtho[1,2-e][1,2,4]triazolo[3,4-c][1,2,4]triazine (10). Acetylation of 9 and 10 gave 3-[N-acetyl-N′-(polyacetoxyalkylidene)hydrazino]acenaphtho[1,2-e][1,2,4]triazine (11) and 1-(polyacetoxyalkyl)acenaphtho[1,2-e][1,2,4]triazolo[3,4-c][1,2,4]triazine (13) respectively. Periodate oxidation of 9e gave 3-(2-oxoethylidenehydrazino)acenaphtho[1,2-e][1,2,4]triazine (14).

LINEAR AND ANGULAR ANALOGUES OF 5‐METHOXYFUROCOUMARIN

AbstractFormation of the furan ring of 5‐methoxyfurocoumarins by cyclization of the corresponding keto‐ether gave angular and linear isomers in ratios varying between 3:1 and 3:2 in favour of the angular isomer. Starting 7‐hydroxy‐5‐methoxy‐4‐methylcoumarin (5) and its 5‐hydroxy‐7‐methoxy isomer (6) were obtained in approximately 1:1 ratio by Pechman reaction of 5‐methoxyresorcinol (4) and ethyl acetoacetate. All products were isolated by flash chromatography and characterized by NOE spectroscopy.

Quinoline Alkaloids. Synthesis of Khaplofoline, Ribalinine, and Flindersine

Reaction of 4-hydroxy-3-prenylquinolin-2(1 H)one (5 a) with iodine and silver acetate gave a iodopyranoquinoline (6 a), which was then converted into the alkaloids khaplofoline (1) and ribalinine (2). Reaction of 5a with iodine and mercuric oxide afforded a mixture of 6a and its angular isomer 7 a; the coversion of latter into flindersine (10) is described.

Possible ecological significance of within-fruit and seed furocoumarin distribution in twoPsoralea species

Furocoumarin distribution patterns in the fruits and seeds ofPsoralea macrostachya andP. onobrychis were investigated. Both species contain the linear furocoumarin psoralen and its angular isomer, angelicin. In the monospermous indehiscent fruit ofP. macrostachya, furocoumarins occur in the pericarp and all seed parts. InP. onobrychis, the pericarp of which is easily detached at ripeness, no furocoumarins were found in the pericarp tissues and only traces occur in the embryo axis; cotyledons are the preferential accumulation site. The within-fruit and -seed furocoumarin variations associated with the developmental stages of fruit were followed inP. onobrychis, in view of changes in the defensive value of the pericarp before and after ripening. Rapid furocoumarin biosynthesis after fertilization was observed in both pericarp and seed; ripening is associated with furocoumarin decrease in the seed and complete disappearance in the pericarp tissues. Such findings are consistent with the chemical defense role of these substances. The cooccurrence of linear and angular isomers seems to be a chemical marker of the genusPsoralea: the biosynthetic pathway leading to the angular isomer as an evolutionary response to selective pressure from herbivore insects is suggested.

Synthesis of 3-(Alditol-1-yl)triazolo[4′,3′:2,3]-1,2,4-triazino[5,6-b]indoles

Abstract A series of the hydrazones were prepared by the reaction of 3-hydrazino-5H-1,2,4-triazino[5,6-b]indole (1) with monosaccharides, and their acetylation was studied. Cyclodehydrogenation of the hydrazones gave 3-(substituted)-10H-1,2,4-triazolo[4′,3′:2,3][1,2,4]triazino[5,6-b]indole, whose acetylation and partial acetylation were carried out. The ring-chain tautomerism of the hydrazones promoted their heterocyclization. The linear structure, and not that of the angular isomer, has been selected for the products. This structure has been confirmed from a model study of the cyclization of the acetaldehyde derivative of 1, which was found to be identical with that product obtained from the reaction of 4,5-diamino-3-methyl-1,2,4-triazole with isatin. Periodate oxidation of the hydrazones and their cyclized products was also studied.

Synthesis of 4',5- and 3',4',5-Oxygenated Pyranoisoflavones: Alpinumisoflavone and Related Compounds, and a Revised Structure of Derrone

Alpinumisoflavone (4',5-dihydroxy-2″,2″-dimethylpyrano [5″,6″- g ] isoflavone) (1a) was synthesized by regioselective reduction of 7-(4-hydroxyphenyl)-2,3-dihydro-5-methoxy-2,2-dimethyl-4H,6H-benzo [1,2-b:5,4-b'] dipyran-4,6-dione (15a) with NaBH 4 and dehydration of the resultant alcohol, followed by demethylation with BCl 3 . Its angular isomer (4',5-dihydroxy-2″,2″-dimethylpyrano [6″,5″-h] isoflavone) (2a) was synthesized from 3-(4-hydroxyphenyl)-8,9-dihydro-5-tosyloxy-8,8-dimethyl-4H,10H-benzo [1,2-b:3,4-b'] dipyran-4,10-dione (27a) is a similar manner