Über Pterinchemie. 57. Mitteilung. Zur Konfiguration und Konformation von 6,7-Dimethyl-und 5,6,7-Trimethyl-5,6,7,8-tetrahydropterin

Configuration and conformation of 6,7-Dimethyl- and 5,6,7-Trimethyl-5,6,7,8-tetrahydropterines. During the hydrogenation of 6,7-dimethylpterine, cis-6,7-dimethyl-tetrahydropterine is formed. A possible conformation for this substance and for the 5,6,7-trimethyl derivative, which is obtained from it, is discussed, taking the ¹H-NMR. spectra of both tetrahydropterines into consideration.     

Über Pterinchemie. 61. Mitteilung. Die Kristallstruktur von 5-Formyl-6,7-dimethyl-5,6,7,8-tetrahydropterin

The crystal structure of 5-formyl-6,7-dimethyl-5,6,7,8-tetrahydropterine The crystal structure of the title compound, a tetrahydropterine, has been determined by X-ray analysis (direct method) and refined with 1579 structure amplitudes to R = 0.054. The crystal system is triclinic, space group P1 , with unit cell dimensions a = 7.171, b = 7.255, c = 12.369 Å, α = 100.64, β = 93.32, γ = 98.27°. The tetrahydropyrazine ring exists in a distinctly flattened conformation. The C(13)- and C(14)-CH₃-groups possess a cis-configuration with axial position for C(13)-CH₃ and equatorial for C(14)-CH₃. The carbonyl-group of the N-formyl function has an (E)-configuration.     

Über Pterinchemie. 56. Mitteilung. Die Kristallstruktur von Xanthopterin-hydrochlorid

The crystal structure of xanthopterine-hydrochloride. The crystal structure of the title compound, a pterine, has been determined by X-ray analysis (direct methods) and refined with 1332 structure amplitudes to R = 0.027. The crystal system is monoclinic, space group P2_1/c, with unit cell dimensions a = 7.942, b = 8.417, c = 12.076 Å, β = 93.77°. The molecule is protonated at the N(1)-position. The angle between the planes of the pyrimidine and pyrazine rings is 2.02°.     

Über Pterinchemie. 49. Mitteilung. Eine neue Synthese von 5-Formyl-6, 7-dimethyl-5,6,7,8-tetrahydropterin und 5,6,7-Trimethyl-5,6,7,8-tetrahydropterin

Starting with 5-formyl-6,7-dimethyl-5,6,7,8-tetrahydropterine (II), a new synthesis of 5,6,7-trimethyl-5,6,7,8-tetrahydropterine (III) is described. Thereby the chemical behaviour of the 5-formyl group in II is investigated, in order to enable the unequivocal differentiation between formylation at position 5 and at position 10 in folic and tetrahydrofolic acid derivatives. ¹³C-NMR. spectra of II and III are discussed.     

Über Pterinchemie. 64. Mitteilung. Die Kristallstruktur von 6-Methyl-7,8-dihydropterin-monohydrochlorid-monohydrat

The crystal structure of 6-methyl-7,8-dihydropterine-monohydrochloride-monohydrate The crystal structure of the title compound has been determined by X-ray analysis (direct methods) and refined with 990 structure amplitudes to R = 0.025. The crystal system is triclinic, space group P1 , with unit cell dimensions a = 5.859, b = 7.686, c = 12.107, α = 71.84, β = 76.35, γ = 85.80. The molecule is protonated at the N(5)-position and is planar. The atoms H(19) and H(20) are with 0.818 Å above respectively with ?0.705 Å under the plane.     

Über Pterinchemie. 59. Mitteilung [1]. Konformationsanalyse von acylierten 5,6,7,8-Tetrahydropterinen

Conformational Analysis of Acylated 5,6,7,8-Tetrahydropterines The conformation of N(5)-acetates, and of N(5)- and N(8)-trifluoroacetates, respectively, of 6-methyl- and cis-6, 7-dimethyl-tetrahydropterines is studied by ¹H-NMR. spectroscopy. It is shown that the methyl group next to the acylated nitrogen atom is in quasi-axial position.     

Über Pterinchemie 75. Mitteilung Synthese von 7-Aminoxanthopterin

Synthesis of 7-Aminoxanthopterin 7-Aminoxanthopterin (II) is obtained in good yield and purity by the transformation of isomer-free xanthopterin-7-carboxylic acid (I) with NH₃ followed by oxidation with MnO₂. The Frontier Orbital Theory contributes to a better understanding of the reaction pathway.     

Über Pterinchemie. 69 Mitteilung [1]. Konformationsanalyse von 5,6,7,8-Tetrahydropteroinsäure und 5,6,7,8-Tetrahydro-L-folsäure

Conformational analysis of 5,6,7,8-tetrahydropteroic acid and 5,6,7,8-tetrahydro-L -folic acid In the 360-MHz-¹H-NMR.-spectrum of (6R, S)-9,9-dideuterio-5, 6, 7, 8-tetrahydropteroic acid (racemic) (XIII) (AMX-System, Fig. 4) and (6R, S)-9,9-dideuterio-5, 6, 7, 8-tetrahydro-L -folic acid (diastereomeric) (XVI) the H_a–C(6) and H_a–C(7) show a vicinal coupling constant of 6,7 Hz and the H_a–C(6) and H_e–C(7) one of 3,2 Hz. The first coupling constant provides evidence for an approximate trans-diaxal arrangement of H_a–C(6) and H_a–C(7), and the second for a gauche conformation of H_a–C(6) and H_e–C(7). The tetrahydropyrazine ring in the racemic 5, 6, 7, 8-tetrahydropteroic acid (III) and in the diastereomeric 5, 6, 7, 8-tetrahydro-L -folic acid (XVII) exists therefore in a half-chair conformation with a pseudoequatorial position of the side chain at C(6) (Fig.5).     

Über Pterinchemie 81. Mitteilung Die Konfiguration an C(6) von natürlichem 5,6,7,8-Tetrahydro-L-biopterin und seinem Pentaacetylderivat

The Configuration at C(6) of Natural 5,6,7,8-Tetrahydro-L-biopterin and of its Pentaacetate The structure of (6.R)-pentaacetyl-5,6,7,8-tetrahydro-L-biopterin, one of two diastereoisomers obtained by catalytic hydrogenation and subsequent acetylation of L-biopterin, has been determined by X-ray diffraction analysis. The space group is P2₁2₁2₁, a=8,053(l), b=14,955(3), c= 21,502 (4) Å. The asymmetric unit contains one molecule of the biopterin derivative and one of ethyl acetate. The R-configuration can be assigned to C(6) by reference to the known configurations of the other asymmetric C-atoms. As hydrolysis of this diastereoisomer yields the natural 5, 6,7,8-tetrahydro-L-biopterin, the latter also possesses the (6 R)-configuration.     

Über Pterinchemie 80. Mitteilung Die Herstellung von (6RS)Tetra- und (6RS)Pentaacetyl-5,6,7,8-tetrahydro-L-bioplerinen

Preparation of (6RS)Tetra- and (6RS)-Pentaacetyl-5,6,7,8-tetrahydro-L-biopterines Boiling of (6RS) l′-O,2′-O,2-N-triacetyl-5,6,7,8-tetrahydro-L-biopterine in acetic anhydride as described in [2], leads to a mixture of the diastereoisomeric (6R)- and (65)-l′-O,2′-O,2-N-,5,8-pentaacetyl-5,6,7,8-L,-biopterines. One of the diastereoisomers can be obtained as pure crystals. It corresponds to the pentaacetate of the natural (6R)- or (6S).,5,6,7,8-tetrahydro-L-biopterine. For the preparation of the earlier described (6RS)- and (6S)-tetraacetyl-tetrahydro-L-biopterines [2] improved conditions are reported.     

Über Pterinchemie. 58. Mitteilung [1]. Sterische Eigenschaften von acylierten 5,6,7,8-Tetrahydropterinen. Rotameren von 5-Trifluoracetyl-tetrahydropterin-Derivaten

Sterochemical Properties of the Acylated 5,6,7,8-Tetrahydropterines. Rotameres of the 5-Trifluoroacetyl-tetrahydropterine Derivatives 6-Methyl- and 6,7-dimethyl-5,6,7,8-tetrahydropterine are acylated with the anhydrides of acetic acid and trifluoroacetic acid. It is shown that the reactivity of the nitrogen otoms increases in the following order: N(3), N(8), N(2′) and N(5). Two rotameres are present in the ¹H-NMR. spectra of the N(5)-trifluoroacetates, but not in those of the N(5)-acetates.     

Über Pterinchemie. 85. Mitteilung. Polyacetylierte 5,6,7,8-Tetrahydro-D- und -L-neopterine. Ein besonderer Fall von N(5)-Alkylierung des 5,6,7,8-Tetrahydroneopterin-Gerüstes

Polyacetylated 5,6,7,8-Tetrahydro-D - and L -neopterins. A Special Case of N(5)-Alkylation of 5,6,7,8-Tetrahydroneopterins Improved conditions are reported for the preparation of the earlier described (6R)- and (6S)-1′-O,2′-O,3′-O,2-N,5-pentaacetyl-5,6,7,8-tetrahydro-L -neopterins, one of which could be obtained as pure crystals. Its structure, determined by X-ray-diffraction analysis, corresponds to the (6R)-enantiomer. The method has also been used to make the corresponding D -diastereoisomers. Further acetylation of (6RS)-1′-O,2′-O,3′-O,2-N-tetraacetyl-5,6,7,8-tetrahydro-D -neopterin under drastic conditions yields a mixture of several polyacetylated D -neopterin derivatives and a polyacetylated ethyl-tetrahydro-D -neopterin which was isolated in crystalline form and established by X-ray-diffraction analysis to be (6R)-1′-O,2′-O,3′-O,4-O,2-N,2-N,8-heptaacetyl-5-ethyl-5,6,7,8-tetrahydro-D -neopterin.     

Über Pterinchemie 76. Mitteilung [1] Eine einfache Synthese von Leucovorin

A Convenient Synthesis of Leucovorin The synthesis of leucovorin, a 5-formyl-(6R or S)-5,6,7,8-tetrahydropteroyl-L -glutamic acid (II) is described. The L -folic acid was first reduced to (6R, S)-tetrahy-dro-L -folic acid (I); formylation with methyl-formate in DMSO gave directly leucovorin (as a diastereomeric mixture) in good yields. To demonstrate, that the formylation occurred regiospecifically at N (5) and not at N (10), N (10)-nitroso-(6 R, S)-tetrahydro-L -folic acid was formylated under the same conditions. Reductive elimination of the N (10)-nitrosogroup gave the identical leucovorin as in the previous case. The synthetic leucovorin was biologically as active as the natural product with Streptococcus faecalis ATCC 8043 and Pediococcus cerevisiae ATCC 8081.     

Über Pterinchemie. 74. Mitteilung. Zum Verlauf der katalytischen Reduktion von 6-Methylpterin

On the Pathway of the Catalytic Reduction of 6-Methylpterin The catalytic hydrogenation of 6-methylpterin (I) in neutral or weekly acidic solution begins, as for the 7-methylpterin, by the thermodynamically controlled reduction of the 7,8-double bond. It is not possible to say, according to our experiments, which double bound, either the 5,6 or the 7,8, is first reduced in strongly acidic solution. However, a 5,8-reduction can be excluded.     

Über Pterinchemie 23. Mitteilung [1]. Radikalbildung während der Oxydation von Tetrahydrofolsäure und 5,6,7,8-Tetrahydropterin

EPR. investigations show the existence of one-electron oxidation of 5,6,7,8-tetrahydropterine and tetrahydrofolic acid resulting in unstable cationic radicals of red color which are trapped at liquid nitrogen temperature.     

Über Pterinchemie. 68 Mitteilung [1]. Regiospezifische Deuterierungen von Folsäure

Regiospecific deuteriation of folic acid Introduction of a nitroso function at the N (10)-position of folic acid activates the C(9)-hydrogen atoms in such a way, that the exchange of H with D at this position, in NaOD-solution, is extremely facilitated. This fact is utilized in the synthesis of 9,9-dideuterio-folic acid (IV), 7,9,9-trideuterio-folic acid (VII) and 7-deuterio-folic acid (IX). These three products are necessary for the ¹H-NMR.-spectroscopical determination of the conformation of 5,6,7,8-tetrahydrofolic acid and its derivatives.     

Über Pterinchemie 18. Mitteilung [1] Monohydro- und Trihydropterin-Radikale

By oxydation of N(5)-methyl-6,7-diphenyl-5,6-dihydro- and N(5)-methyl-6,7-diphenyl-5,6,7,8-tetrahydro-pterine derivatives with perhydrol 8-monohydro- and 6,7,8-trihydro-pteridine radical cations are produced which are sufficiently stable for detection and structural elucidation by ESR. hyperfine analysis. The biological implications of these radicals for pteridine dependent hydroxylation and methyl transfer from 5-methylfolinic acid are discussed.