Ferrocene-modified guanosine derivatives: Synthesis and characterization

In this paper, we report the first modification of guanosine with a ferrocene (Fc) group using Stille and Sonogashira cross-coupling reactions of 8-bromoguanosine and tri-n-butylstannyl ferrocene or ethynylferrocene, respectively. The two resulting Fc-guanosine conjugates were fully characterized spectroscopically and their electrochemical properties were characterized cyclic voltammetry showing more anodic oxidations due to electronic coupling between the Fc group and the nucleobase.     

Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-e-imidazolecarboxamide. IV. A new route to guanosine via cyanamide derivative.

4-Cyanamido-5-imidazolecarboxamide (IV) was prepared by brief treatment of 5-(S-methylisothiocarbamoyl) amino-4-imidazolecarboxamide (V) with alkali. Compound VI was converted in an alkaline solution to either guanine (VII) or isoguanine (VIII), depending on the concentration of alkali. This procedure was applied to the synthesis of 2',3'-0-isopropylideneguanosine (XVI) from the riboside of 5-(N'-benzoyl-S-methylthiocarbamoyl) amino-4-imidazolecarboxamide (IX), PROviding a new route to XVI.     

Conformation of acetylaminofluorene and aminofluorene modified guanosine and guanosine derivatives

Acetylaminofluorene and aminofluorene modified Guo, GMP, d(GpA) and d(ApG) have been studied by circular dichroism and ¹H nuclear magnetic resonance. Aminofluorene modified Guo is preferentially in the $\text{anti}$ conformation and acetylaminofluorene modified Guo in the $\text{syn}$ conformation. It is proposed that the $\text{anti}$ conformation of aminofluorene modified Guo is stabilized by an intra molecular hydrogen bond between the NH group of aminofluorene residue and the 5′-OH group of the sugar. The results on the modified dinucleoside monophosphates are analyzed according to this hypothesis.     

Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide. III. Formation of a novel cycloimidazole nucleoside and its cleavage reactions.

A new cycloimidazole nucleoside, 5-(1 inch -benzamido-1 inch-hydroxymethylene) amino-2', 1 inch-anhydro-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (III) was synthesized by reaction of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with benzoyl isothiocyanate followed by methylation with methyl iodide. The structure of III was elucidated on the basis of its nmr spectra and chemical reactions. Of special interest are reactions of III with various nucleophiles. For example, guanosine (IX) was obtained by amination of III wtih ammonia in 72% yield. Analogous reactions of III with methylamine and dimethylamine gave N2-methylguanosine (X) and N2-dimethylguanosine (XI), respectively. Refluxing of III in alkaline solution afforded xanthosine (VII). The probable mechanism of formation and facile ring-opening of III is also discussed.     

Alkaline stability of guanosine and some of its derivatives modified by the carcinogen N-acetoxyacetylaminofluorene.

The alkaline treatment of Guo, dGuo, dGMP and denatured DNA modified by N-acetoxyacetylaminofluorene (N-AcO-AAF) was performed in 0.1 M NaOH at 40 degrees C. The kinetics of the reaction were followed by ultraviolet absorption and by chromatographic methods and were found different for the four products under study. Circular dichroism spectra show differences in the environment of acetylaminofluorene residue in these products. The alkaline treatment of Guo-AAF (and dGuo-AAF) leads to the formation of three products. These products were separated by thin layer chromatography and by HPLC and were characterized by spectroscopic methods. One is the already known unstable Guo-AF (and respectively dGuo-AF) (1). The other two products are relatively stable products of the transformation of Guo-AF (or dGuo-AF). These last ones present almost identical ultraviolet absorption spectra, but very different circular dichroism spectra.     

Affinity of guanosine derivatives for polycytidylate revisited

Evidence is presented for complexation of guanosine 5-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23°C in the presence of 1.0 M NaCl and 0.2 M MgCl₂ in water. The association of 2-McImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) · 2-McImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-McImpG equal to 5.55 ± 0.15 mM at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5-monophosphate (5GMP), guanosine 5monophosphate imidazolide (ImpG), and guanosine 5monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-McImpG.     

Synthesis of penaresidin derivatives and its biological activity

A series of stereoisomers for the azetidine ring of penaresidin B was synthesized and their cytotoxic and antimicrobial activities were evaluated. Among six synthetic isomers 1-6, isomers 4 and 5 showed relatively potent cytotoxic activity against A549 (lung) and HT29 (colon) tumor cells as well as antibacterial activity.     

Synthesis and enzymic activity of 8-acyl and 8-alkyl derivatives of guanosine 3, 5-cyclic phosphate.

Several new 8-alkyl and 8-acyl derivatives of quanosie 3',5'-cyclic phosphate (cGMP) and inosine 3',5'-cyclic phosphate (cGMP) were prepared by direct alkylation or acylation of the parent cyclic nucleotide via free radicals generated in situ. These compounds have been examined for their ability to stimulate a cGMP-dependent protein kinase, and several of the cGMP derivatives were as active in this regard as cGMP. These compounds proved to be quite ineffective when tested for their ability to activate an adenosine 3',5'-cyclic phosphate (cAMP) dependent protein kinase. In addition, these 8-substituted cGMP derivatives are not substrates for a phosphodiesterase preparation from rabbit kidney, but do show inhibition of the hydrolysis of cAMP by crude phosphodiesterase preparations from rabbit lung and beef heart.     

Synthesis of novel quinoxaline derivatives and its cytotoxic activities

Substituted dihydroquinozalin-2-ones (1–16) have been synthesized easily by the use of copper-catalyzed coupling method. The reactions of 2-haloanilines with a variety of α-amino acids in the presence of copper (I) iodide gave corresponding 3-substituted dihydroquinozalin-2-ones in up to 86% yield. Some new quinoxalin-2-ones (2, 4, 5, 13 and 16) have moderate cytotoxic activity toward HeLaS3 cell lines at 4.9–18.1 μM.     

Synthesis and structure-immunosuppressive activity relationships of bakuchiol and its derivatives

A series of derivatives of bakuchiol were synthesized and tested in vitro for their cytotoxicity, and inhibition of T cell proliferation and B cell proliferation. The data obtained provided preliminary structure-activity relationships of the compounds as immunosuppressive activity.     

Synthesis of l-idofuranurono-6,3-lactone and its derivatives via hexodialdodifuranoses

1,2-O-Alkylidene-β-l-idofuranurono-6,3-lactones were obtained from the corresponding 5-O-toluene-p-sulphonyl-α-d-glucofuranurono-6,3-lac tones by a sequence involving lactone reduction, benzoylation of HO-6, inversion of configuration at C-5, deacylation, and lactol oxidation. Hydrogenolysis or methanolysis of 1,2-O- benzylidene-β-l-idofuranurono-6,3-lactone gave l-idofuranurono-6,3-lactone and a mixture of its methyl glycosides, respectively.     

Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives

One of the known cytotoxic lignans is (-)-1-O-feruloyl-secoisolariciresinol designated as hanultarin, which was isolated from the seeds of Trichosanthes kirilowii. In this Letter, we described the first synthesis of 1-O-feruloyl-secoisolariciresinol, 1,4-O-diferuloyl-secoisolariceresinol and their analogues. The cytotoxicities of these compounds were evaluated against several cancer cell lines. Interestingly, we found that the feruloyl diester derivative of secoisolariciresinol was the most active cytotoxic compound against all the cancer cells tested in this experiment. The IC(50) values of the1,4-O-diferuloyl-secoisolariceresinol were in the range of 7.1-9.8μM except one cell line. In considering that both ferulic acid and secoisolariciresinol are commonly found in many plants and have no cytotoxicity, this finding is remarkable in that simple covalent bonds between the ferulic acid and secoisolariciresinol cause a cytotoxic effect.     

Interaction of metal ions with nucleic acids. Interaction of copper(II) with guanosine and its derivatives.

Interaction of copper(II) with guanosine, 2'-deoxyguanosine, 1-methylguanosine, 7-methylguanosine and GMP was studied withe use of spectroscopic and magneto-chemical methods. The main site of copper(II) binding in guanosine is nitrogen N-7; participation of N-1 is not excluded. The involvement of carbonyl oxygen in copper binding or copper chelation to N-7 and 0-6 is rather unlikely. A crystalline complex of copper(II) with GMP [Cu(C10H12O8N5P) .(H2O)3] was obtained, and it was demonstrated that copper(II) is bound with N-7 and the phosphate group.     

Detection and identification of mutagens and carcinogens as their adducts with guanosine derivatives

For use in screening for environmental mutagens and carcinogens, a highly fluorescent derivative of guanosine, 2'-deoxy-2'-(2",3"-dihydro-2",4"-diphenyl-2"-hydroxy-3"-oxo-1"-pyrrol yl) guanosine (FG), was synthesized. When incubated with FG in aqueous solution, mutagens form adducts that can be analyzed with an HPLC-fluorescence detector-system. By this method, mutagens such as glyoxal, methylglyoxal, 2-(2-furyl)-3-(5-nitrofuryl) acrylamide and 4-nitroquinoline-N-oxide, used as model compounds, were detected rapidly with high sensitivity. Reaction with isopropylideneguanosine (IPG), followed by isolation and characterization of the mutagen-IPG-adduct was found to be a useful method for identifying unknown mutagens in crude samples. This method was successfully applied in identification of the mutagens in heated glucose (200 degrees C, 20 min); glyoxal-IPG and 8-hydroxy-IPG were identified in the reaction mixture.     

Synthesis of 8-diamino-substituted adenosine, inosine, and guanosine

Adenosine, inosine and guanosine derivatives were prepared, modified at the C-8 atom with the aid of diamines (1,3-diaminopropane, 1,4-diaminobutane and 1,5-diaminopentane).