Anura Wickramasinghe

Syntheses of carboncarbon linked carboranylated porphyrins for boron neutron capture therapy of cancer

Abstract Total syntheses of six carboranyl-containing porphyrins bearing 33–44% boron by weight for potential application in boron neutron capture therapy of tumors, are described; these novel compounds feature carboncarbon linkages between the carboranyl groups and the meso -phenyl substituents.

Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice

The total synthesis of a 5,15-di[3,5-(o-carboranylmethyl)phenyl]porphyrin 5, its zinc(II) complex 6, and the corresponding nido-carboranylporphyrins 7 and 8 are reported. The molecular structures of porphyrin 6 and of potassium nido-carborane were obtained and are described. The biodistribution of nido-carboranylporphyrins 7 and 8 in BALB/c mice bearing EMT-6 mammary tumors are presented and compared. Both compounds are effective tumor localizers and delivered therapeutic concentrations of boron to tumors (mean+/-standard deviation): 32.5+/-7.1 and 54.3+/-14 microg/g for 7 and 8, respectively, 2 days after the last of 3 injections of a total boron dose of 23 mg/kg body weight. The zinc(II) complex 8 was found to deliver 1.2-1.7 times higher amounts of boron to tumors than 7, with lower tumor-to-blood boron concentration ratios (9.8/1 and 4.7/1 for 7 and 8, respectively, 2 days after injections). The tumor-to-brain boron concentration ratios were >100/1 for both porphyrins 2 days after administration. Both nido-carboranylporphyrins 7 and 8 were well-tolerated at the concentrations used (75 and 78 mg/kg body weight, respectively) and no morbidity or mortality were observed in these studies.

Investigations on the directive effects of a single meso-substituent via nitration of 5,12,13,17,18-pentasubstituted porphyrins: syntheses of conjugated β-nitroporphyrins

Abstract Vilsmeier formylation of 5-substituted 1,9-diunsubstituted dipyrromethanes afforded 1,9-diformyldipyrromethanes in good yields. Their MacDonald condensation with tetra-β-alkyldipyrromethanes produced 5,12,13,17,18-pentasubstituted porphyrins. A meso-electron-donating group, presumably acting by destabilizing the porphyrin a2u ground state, directs the nitrations to the meso-carbons. β-Nitration takes place on porphyrins bearing a meso-electron-withdrawing group. Unhindered β-nitro groups are shown to exert stronger electronic effects relative to meso-nitro groups by conjugating effectively with the porphyrin macrocycle.

Natural product chemistry, part 137: Oxidation of acridone alkaloids: Synthesis of 5-methoxyacronycine

SummaryEpoxidation of the acridone alkaloid acronycine (1) resulted in hydroxylation at the aromatic ring giving 5-hydroxyacronycine (3). The same reaction on 1,3-dimethoxy-10-methyl-9(10H)-acridinone (5) gave 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (6), 1,3-dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)-acridinone (8), and 1,3-dimethoxy-2,4-diperoxy-10-methyl-9(10H)-acridinone (9).ZusammenfassungDie Epoxidierung des Acridonalkaloids Acronycin führte zu einer Hydroxylierung des aromatischen Rings, wobei 5-Hydroxyacronycin (3) entstand. Die gleiche Reaktion mit 1,3-Dimethoxy-10-methyl-9(10H)acridinon (5) ergab 1,3-Dimethoxy-2-hydroxy-10-methyl-9(10H)acridinon (6), 1,3-Dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)acridinon (8) und 1,3-Dimethoxy-2,4-diperoxy-10-methyl-9(10H)acridinon (9).

Antioxidant Constituents from Xylopia championii.

Abstract Xylopia championii. Hook. f. & Thoms. (Annonaceae) is endemic to Sri Lanka. The antioxidant and antifungal activities of five alkaloids, oxopurpureine, (+)-laudanidine, (−)-discretine, nordicentrine, and dehydrocorytenchine, isolated from the stem bark and stem of X. championii., were studied. The alkaloids, (+)-laudanidine and (−)-discretine, at a concentration of 0.5 mg/mL, exhibited exceptionally high antioxidant activity, where as nordicentrine and dehydrocorytenchine showed moderate activity as compared with the standard antioxidant dl-α -tocopherol in the DPPH assay. All five alkaloids were subjected to an antifungal bioassay against Clodosporium cladosporioides.. Nordicentrine showed the most potent antifungal activity at 6 μ g/spot, and (-)-discretine showed moderate activity at 30.0 μg/spot.

Singlet oxygen generation and dark toxicity of a nido- and a closo-carboranylporphyrin

The dark toxicity and singlet oxygen quantum yields of the zinc(II) complexes of the nido- and closo-carboranylporphyrins 4 and 5 are reported. Both carboranylporphyrins show very low toxicity towards V79 hamster lung fibroblast cells (IC50 > 500 μM), display similar absorption and fluorescence emission spectra, and are efficient producers of singlet oxygen (quantum uilds of 0.72 in CD3OD and 0.45 in CHCl3 were determined for 4 and 5, respectively). Our results indicate that the presence of nido- or closo-carborane cages bound via methylene linkages to the meso-phenyl groups, do not substantially alter the photosensitizing properties of porphyrin macrocycles. It is suggested that carboanylporphyrins could have dual application in the boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) treatment of malignant brain tumors.

Two phenylpropanoids from Flindersia australis stem wood

Abstract Two new phenylpropanoids, 4′-(3″-methylbut-2″-enyloxy)-3-phenylpropanol and 4′-(3″-methyl-4″-hydroxybutyloxy)-3-phenylpropanol were isolated together with the coumarin, seselin from the stem wood of Flindersia australis .

Natural product chemistry. Part 121. Synthesis of dicoumarinyl ethers with the structures proposed for fatagarine and oreojasmine

Synthesis of the 7,8′-dicoumarinyl ethers: 7-methoxy-7′,8-oxydicoumarin and 6,7-dimethoxy-7′,8-oxydicoumarin, established that the structures of fatagarine and oreojasmine for which these two structures have been proposed, have to be revised. Synthesis of 7-methoxy-5,7′-oxydicoumarin and 8-methoxy-7,7′-oxydicoumarin exclude the possibility of these dicoumarinyl ether structures for fatagarine.ZusammenfassungDurch die Synthese der 7,8-Dicumarinylether: 7-Methoxy-7′,8-oxydicumarin und 6,7-Dimethoxy-7′,8-oxydicumarin, ließ sich nachweisen, daß die für das Fatagarin und Oreojasmin vorgeschlagenen Strukturen revidiert werden müssen. Die Darstellung des 8-Methoxy-7,7′-oxydicoumarin und 7-Methoxy-5,7′-oxydicumarin schließen die Möglichkeit dieser Strukturen für das Fatagarin aus.

Synthesis, characterization and photochemistry of 5,10,15,20-tetrakis(4-N-pentylpyridyl)porphyrins, [(TPePyP)H2]4+ and [(TPePyP)ZnII]4+

Tetracationic 5,10,15,20-tetrakis(4-N-pentylpyridyl)porphyrins, [(TPePyP)H2]4+ and its zinc-porphyrin analogue [(TPePyP)ZnII]4+ have been synthesized and characterized by 1H NMR and UV-visible spectroscopic techniques. Photobleaching studies carried out in solutions of varying pH show that, in the presence of oxygen, [(TPePyP)H2]4+ undergoes fast photodegradation in aqueous medium when the solution is irradiated with 560 nm light. The steady-state singlet oxygen quantum yields (ΦΔ) for [(TPePyP)H2]4+ is 0.80 and that for its Zn analogue is 0.85. These quantities were measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen scavenger, in N,N-dimethyl-formamide solution. These ΦΔ values are compared with those for other well known sensitizers such as protoporphyrindimethylester PPDME and hematoporphyrindihydrochloride HPDHC.

Natural product chemistry, part 136: A convenient synthesis of rutacridone and isorutacridone

SummaryC-alkylation of phenolic acridones with 1,4-dibromo-2-methyl-2-butene under different conditions was studied. Condensations with 1,3 dihydroxy-10-methyl-acridin-9(10H)-one gave an O-alkylated product together with rutacridone and isorutacridone through C-alkylation. The aluminiumoxide and the ion exchange resin method offered the best yields for rutacridone and isorutacridone, respectively. Attempts with 4-hydroxy-10-methylacridin-9(10H)-one yielded several O-alkylated products including a dimer.ZusammenfassungDie C-Alkylierung von phenolischen Acridonen mit 1,4-Dibrom-2-methyl-2-buten wurde unter verschiedenen Bedingungen studiert. Die Kondensation mit 1,3-Dihydroxy-10-methylacridin-9(10H)-on ergibt ein O-alkyliertes Produkt zusammen mit Rutacridon und Isorutacridon, die über eine C-Alkylierung entstehen. Die Aluminiumoxid- und die Ionenaustauscher-Methode lieferten die besten Ausbeuten an Rutacridon und Isorutacridon. Versuche mit 4-Hydroxy-10-methyl-acridin-9(10H)-on führten zu einigen O-alkylierten Produkten, darunter ein Dimeres.