4271-30-1Relevant articles and documents
Reactivity of conjugated and unconjugated pterins with singlet oxygen (O2(1Δg)): Physical quenching and chemical reaction
Cabrerizo, Franco M.,Laura Dantola,Petroselli, Gabriela,Capparelli, Alberto L.,Thomas, Andres H.,Braun, Andre M.,Lorente, Carolina,Oliveros, Esther
, p. 526 - 534 (2007)
Pterins (PTs) belong to a class of heterocyclic compounds present in a wide range of living systems. They participate in relevant biological functions and are involved in different photobiological processes. We have investigated the reactivity of conjugated PTs (folic acid [FA], 10-methylfolic acid [MFA], pteroic acid [PA]) and unconjugated PTs (PT, 6-hydroxymethylpterin [HPT], 6-methylpterin [MPT], 6,7-dimethylpterin [DPT], rhamnopterin [RPT]) with singlet oxygen (1O2) in aqueous solutions, and compared the efficiencies of chemical reaction and physical quenching. The chemical reactions between 1O2, produced by photosensitization, and PT derivatives were followed by UV-visible spectrophotometry and high-performance liquid chromatography, and corresponding rate constants (kr) were evaluated. Whenever possible, products were identified and quantified. Rate constants of 1O2 total quenching by the PT derivatives investigated were obtained from steady-state 1O2 luminescence measurements. Results show that the behavior of conjugated PTs differs considerably from that of unconjugated derivatives, and the mechanisms of 1O2 physical quenching by these compounds and of their chemical reaction with 1O2 are discussed in relation to their structural features.
Effect of pterin impurities on the fluorescence and photochemistry of commercial folic acid
Dántola, M. Laura,Urrutia, M. Noel,Thomas, Andrés H.
, p. 157 - 163 (2018)
Folic acid, or pteroyl?L?glutamic acid (PteGlu) is a conjugated pterin derivative that is used in dietary supplementation as a source of folates, a group of compounds essential for a variety of physiological functions in humans. Photochemistry of PteGlu is important because folates are not synthesized by mammals, undergo photodegradation and their deficiency is related to many diseases. We have demonstrated that usual commercial PteGlu is unpurified with the unconjugated oxidized pterins 6?formylpterin (Fop) and 6?carboxypterin (Cap). These compounds are in such low amounts that a normal chromatographic control would not detect any pterinic contamination. However, the fluorescence of PteGlu solutions is due to the emission of Fop and Cap and the contribution of the PteGlu emission, much lower, is negligible. This is because the fluorescence quantum yield (ΦF) of PteGlu is extremely weak compared to the ΦF of Fop and Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation photosensitized by oxidized unconjugated pterins present in the solution, and not a process initiated by the direct absorption of photons by PteGlu. In brief, the fluorescence and photochemical properties of PteGlu solutions, prepared using commercially available solids, are due to their unconjugated pterins impurities and not to PteGlu itself. This fact calls into question many reported studies on fluorescence and photooxidation of this compound.
Unexpected photoactivation pathways in a folate-receptor-targetedtrans-diazido Pt(iv) anticancer pro-drug
Gandioso, Albert,Marchán, Vicente,Rovira, Anna,Sadler, Peter J.,Shi, Huayun
, p. 11828 - 11834 (2020)
A conjugate between a photoactivetrans-diazido Pt(iv) pro-drug,trans,trans,trans-[Pt(N3)2(OH)2(py)2], and folic acid has been synthesized and fully characterized by high resolution ESI-MS, NMR and UV-vis spectroscopy. Photoactivation of the Pt-folate conjugate with visible light confirmed the generation of cytotoxic Pt(ii) species capable of binding to guanine nucleobases. Importantly, photoreduction of the Pt(iv) complex triggered the photodecomposition of the folate vector into ap-aminobenzoate-containing fragment and several pterin derivatives, including 6-formylpterin. Besides exhibiting high dark stability in physiological-like conditions, the Pt-folate conjugate wasca. 2× more photocytotoxic towards MCF-7 breast cancer cell line than its parent Pt(iv) complex with a high photoselectivity index (PI > 6.9). The higher photocytotoxicity of the conjugate may be a consequence of its higher cellular accumulation and of the generation of a set of different cytotoxic species, including Pt(ii) photoproducts and several pterin derivatives, which are known to generate ROS.
Influence of human serum albumin on photodegradation of folic acid in solution
Vorobey, Pavel,Steindal, Arnfinn Engeset,Off, Morten Kristian,Vorobey, Alexander,Moan, Johan
, p. 817 - 822 (2006)
It has been proposed that photodegradation of folates may be the reason for the pigmentation of races living under high fluence rates of ultraviolet radiation. The photodegradation of folic acid (FA) induced by ultraviolet-A (UV-A) radiation, in solution and in the presence of human serum albumin (HSA), was studied with absorption and fluorescence spectroscopy. FA photodegradation, with formation of p-aminobenzoyl-L-glutamic acid, 6-formylpterin and pterin-6-carboxylic acid, was found to follow an exponential trend. A scheme of FA photodegradation, which involves photosensitization of FA degradation by its photoproducts, was proposed. The rate of FA photodegradation decreased drastically in the presence of HSA, whereas the spectral characteristics of the photoproducts remained constant. The reduction of the FA photodegradation rate by HSA was accompanied by degradation of tryptophan in HSA. Tryptophan, when added to solutions of FA, had a similar effect as HSA. In solutions of FA and HSA the FA photoproducts cause photodamage mainly to HSA rather than to FA itself. The oxygen dependence of FA photodegradation and the inhibition of this process by sodium azide indicate that singlet oxygen may participate in the photosensitizing activity of FA photoproducts.
Preparation method of N-p-aminobenzoyl-L-glutamic acid
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Paragraph 0015; 0019; 0020; 0021; 0022; 0024, (2018/07/15)
The invention discloses a preparation method of N-p-aminobenzoyl-L-glutamic acid. The preparation method comprises the following steps of: (1) adopting p-nitrobenzoic acid as a starting material, adopting oxalyl chloride as an acylating chlorination reagent, adopting tetrahydrofuran and DMF (Dimethyl Formamide) as a mixed solvent, and carrying out acylating chlorination reaction to prepare paranitrobenzoyl chloride; (2) carrying out condensation reaction of the paranitrobenzoyl chloride prepared in the step (1) and sodium glutamate to prepare N-p-nitrobenzoyl-L-glutamic acid; (3) adopting hydrazine hydrate as a reducing agent, adopting ferric trichloride hexahydrate as a catalyst, and carrying out reducing reaction of the N-p-nitrobenzoyl-L-glutamic acid prepared in the step (2) to preparethe N-p-aminobenzoyl-L-glutamic acid. The preparation method disclosed by the invention has the beneficial effects that the acylating chlorination reaction selects the oxalyl chloride as the acylating chlorination reagent in the mixed solvent of the tetrahydrofuran and the DMF, the reducing reaction selects the hydrazine hydrate as the reducing agent and selects the ferric trichloride hexahydrateas the catalyst, and finally the N-p-aminobenzoyl-L-glutamic acid with the purity being more than or equal to 99.9% can be obtained.
Preparation method of N (4-aminobenzoyl)-L-glutamic acid
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Paragraph 0029; 0030, (2016/10/31)
The invention provides a preparation method of N (4-aminobenzoyl)-L-glutamic acid. According to the method, p-nitrobenzoic acid is taken as a raw material, BTC/C2H4Cl1 is taken as an acylating chlorination agent, DMF (dimethyl formamide) is added to serve as an initiator, and p-nitrobenzoyl chloride is prepared through reaction at a reflux temperature; p-nitrobenzoyl chloride and sodium glutamate have condensation, and N-(4-nitrobenzoyl)-L-glutamic acid is prepared; N-(4-nitrobenzoyl)-L-glutamic acid is reduced by Pd/C/HCO2NH4, and N (4-aminobenzoyl)-L-glutamic acid is prepared. The preparation method has mild reaction conditions and is simple in process, easy to operate and suitable for industrial production; few three wastes are generated, and a product has high purity and high yield.
Resolution of (±)-β-methylphenylethylamine by a novel chiral stationary phase for Pirkle-type column chromatography
Yilmaz, Hayrullah,Topal, Giray,Cakmak, Resit,Hosgoren, Halil
experimental part, p. 252 - 257 (2010/12/18)
In this study, a new Pirkle-type chiral column stationary phase for resolution of β-methylphenylethyl amine was described by using activated Sepharose 4B as a matrix, L-tyrosine as a spacer arm, and an aromatic amine derivative of L-glutamic acid as a ligand. The binding capacities of the stationary phase were determined at different pH values (pH = 6, 7, and 8) using buffer solutions as mobile phase, and enantiomeric excess (ee) was determined by HPLC equipped with chiral column. The ee was found to be 47%.
Photodegradation of 5-methyltetrahydrofolate: Biophysical Aspects
Steindal, Arnfinn Hykkerud,Juzeniene, Asta,Johnsson, Anders,Moan, Johan
, p. 1651 - 1655 (2008/02/13)
5-methyltetrahydrofolate (5MTHF) absorbs UV radiation and has an absorption coefficient of 24250 ± 1170 M-1 cm-1 at 290 nm. It has a weak fluorescence emission in the wavelength region around 360 nm. Our data demonstrated induction of 5-methyldihydrofolate by exposure to UVB and, after continues irradiation, p-aminobenzoyl-L-glutamic acid was found. The photodegradation of 5MTHF follows a first order kinetic with a degradation rate constant of 9.2 × 10-3 min-1 under our conditions (fluence rate of 2.15 mW cm-2, exposure wavelengths from 280 to 350 nm). Our results indicate that a direct degradation of 5MTHF by UV exposure in humans in vivo is rather unlikely. 5MTHF mainly absorbs, and is degraded by, UVB and UVC, radiation that does not penetrate the earth's atmosphere and the human skin well.
Possible role of hydroxyl radicals in the oxidative degradation of folic acid
Patro, Birija S.,Adhikari, Soumyakanti,Mukherjee, Tulsi,Chattopadhyay, Subrata
, p. 67 - 71 (2007/10/03)
An unprecedented .OH radical-induced N-dealkylation of amines including folic acid is reported, the reaction proceeding via a direct hydrogen atom abstraction mechanism as revealed by pulse radiolysis experiments. Hydroxyl radicals have been found to cause oxidative N-dealkylation of amines including folic acid via a hydrogen atom transfer mechanism.
The synthesis of folic acid, multiply labelled with stable isotopes, for bio-availability studies in human nutrition
Maunder, Peter,Finglas, Paul M.,Mallet, Anthony I.,Mellon, Fred A.,Aaqib Razzaque,Ridge, Brian,Vahteristo, Liisa,Witthoeft, Cornelia
, p. 1311 - 1323 (2007/10/03)
Two different methods for the synthesis of folic acid, which are suitable for the incorporation of compounds multiply labelled with stable isotopes, are described. The first method is based on the use of a novel reductive amination to link 2-acetyIamino-4-hydroxy-6-formylpteridine withp-aminobenzoyl-L-glutamic acid. The second method is based on the penultimate formation of an amide bond between Ar-2-acetyl-Ar-10-trifluoroacetyIpteroic acid and dimethyl L-glutamate. Both methods have been used to transform [13C6]aniline into folic acid, labelled with [13C6] in the p-aminobenzoate moiety, and [3,3,4,4-2H4]-L-glutamic acid into folic acid, labelled with [2H4] in the glutamate moiety. Doubly labelled [13C6,2H 4]-p-aminobenzoyl-L-glutamate has also been prepared by the former method.
