Reactions of furocoumarins. II. Synthetic aminomethyl psoralens via chloromethylation or benzylic bromination

Several psoralen derivatives have been synthesized in order to evaluate their efficacy as photochemotherapeutic (PUVA) agents, including a variety of 4′-substituted-4,5′,8-trimethypsoralen compounds ( 1d-j ). Improved synthesis of the very potent photosensitizers 8-methylpsoralen ( 6a ) and 4,8-dimethylpsoralen ( 6b ) are described and 6a has been shown to undergo formylation in the 4′-position. Free radical bromination of 6a and 6b with NBS affords primarily 8-bromomethyl derivatives ( 8a and d ), which are readily converted into the 8-aminomethyl derivatives ( 8c and f ) by the Gabriel method. If the 4′-position is blocked, electrophilic substitution apparently occurs primarily in the 5′-position of the psoralen system. At least, chloromethylation of 4′-methylpsoralen ( 9 ) affords mainly 5′-chloromethyl derivatives ( 10a and d ), which also lead to aminomethylpsoralens ( 10c and f ).     

Fluorescence lifetimes of furocoumarins. Psoralens

The fluorescence lifetimes of linear furocoumarin drugs and model compounds are reported in water, ethanol and water/ethanol mixtures. In most cases more than one lifetime is observed and this is discussed in terms of complex and excited-state complex formation between the solvent and furan moiety of the drugs.     

Modified coumarins. 24. Synthesis of cycloheptane-annellated tetracyclic furocoumarins

Substituted 2,3,4,5-tetrahydrocyclohepta[c]furo[3,2-g]chromen-6-ones, modified psoralen analogs containing a cycloheptane ring annellated to the 5,6-positions of a furo[3,2-g]chromen-7-one, were synthesized from 3-hydroxy-8,9,10,11-tetrahydrocyclohepta[c]chromen-6-ones. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 534–540, November–December, 2006.     

Photoreactions of furocoumarins with biomolecules

Recent aspects of the photoreactions of linear and angular furocoumarins with DNA and related compounds, including [2 + 2] cycloaddition to pyrimidine bases, covalent attachment to the osidic moiety of adenine nucleosides and photodynamic effects, are surveyed. Reactions of photoexcited furocoumarins with proteins and unsaturated lipids and the possible biological roles of the resulting adducts are also presented and discussed.     

Aminomethyl psoralens. Electrophilic substitution of hydroxymethylphthalimide on linear furocoumarins

A new synthetic route to aminomethylpsoralens, substituted on the furan-ring, has been developed by electrophilic substitution of N-hydroxymethylphthalimide and subsequent hydrazinolysis. Hydroxy and methoxy activating functions on the psoralens lead to multi-site substitution and the products of these phthalimido-methylations resist simple cleavage with hydrazine. The two-step introduction of a single CH₂NH₂ group is successful in psoralens containing only methyl substituents.     

Plant coumarins: XIII. Synthesis of 2,3,9-trisubstituted furocoumarins

Peucedanin reacted with methylideneiminium salt generated in situ from N,N,N′,N′-tetramethylmethanediamine and acetyl chloride to give 2-(dimethylaminomethyl)oreoselone. Reactions of peucedanin with aminomethylating agents generated in situ from formaldehyde and dimethylamine, N-methylpiperazine, or N-Boc-piperazine in boiling methanol smoothly afforded the corresponding 9-aminomethyl derivatives whose hydrolysis produced 9-aminomethyl-substituted oreoselones. 2,3,9-Trisubstituted linearly fused furocoumarins were synthesized by reactions of 9-substituted oreoselone trifluoromethanesulfonates with arylboronic acids.     

NMR study of some coumarins and furocoumarins methylated

The ¹H and ¹³C NMR spectra of various methylcoumarins and methylfurocoumarins are reported. All signals were assigned and the influence on chemical shifts of methylation at various positions was determined.     

Synthetic and modified isoflavonoids. I. Synthetic analogues of pseudo-baptigenin

New isoflavones derived from pseudobaptigenin containing alkyl substituents in position 6 have been synthesized. The structures of the compounds have been confirmed by PMR and IR spectroscopies.Taras Shevchenko Kiev University KIEN. and Karakalpak Division. Academy of Sciences of the Republic of Uzbekistan, Nukus. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 669–674, September–October, 1993.     

Synthetic and modified isoflavonoids. I. Synthetic analogues of pseudo-baptigenin

New isoflavones derived from pseudobaptigenin containing alkyl substituents in position 6 have been synthesized. The structures of the compounds have been confirmed by PMR and IR spectroscopies.     

One-pot synthesis of furocoumarins through cascade addition-cyclization-oxidation

A novel one-pot cascade addition-cyclization-oxidation for the regioselective synthesis of furo[3,2-c]coumarins has been developed; the reaction is mild and easily handled without the necessity for dry solvents and inert atmosphere.     

Photosensitization and phototherapy with furocoumarins: A quantum-chemical study

The effect of electromagnetic radiation on biological objects extends from heating to complex photochemistry, and includes DNA alteration, that properly modified in damaged cells may entail beneficial effects. In this regard, psoralen + UV-A (PUVA) therapy, in which furocoumarins, psoralen-like chromophores, are used as photosensitizers and photoreactants with DNA bases, is one of the most promising strategies against a plethora of diseases. Understanding the underlying photochemical mechanisms is crucial to design effective drugs without undesired side effects. We have undertaken a quantum-mechanical study on the photophysics and photochemistry of furocoumarins, analyzing firstly the most efficient way in which the lowest excited triplet state, as protagonist of the photosensitizing action, is populated from the initially promoted singlet states, and secondly the basics of the formation of furocoumarin–DNA photoadducts.     

Coumarins and furocoumarins from the fruit of Prangos uloptera

Chemistry of Natural Compounds -