Über Pterinchemie 51. Mitteilung [1] CNDO-Rechnungen an Pterin, 6,7-Dimethyl-7,8-dihydropterin und 5-Formyl-6, 7-dimethyl-5,6,7,8-tetrahydropterin

The ¹³C-NMR.-spectra of 7,8-dihydropterines and 5,6,7,8-tetrahydropterines show a large difference in the chemical shifts of the 4a- and 8a-sp²-carbon atoms. From the CNDO calculations it is apparent that there is a considerable difference in electron density at C(4a) and C(8a) atoms, which leads to a strong polarity of the C? C-Bond. The electron distribution in the highest occupied molecular orbital (HOMO) is discussed.     

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. 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 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.     

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. 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. 73. Mitteilung [1]. Zum Verlauf der katalytischen Reduktion von 7-Methylpterin

On the Pathway of the Catalytic Reduction of 7-Methylpterin The catalytic hydrogenation of 7-methylpterin (VII) in a neutral solution occurs first by the reduction of the 7,8-double bond (thermodynamically-controlled reaction) followed by the reduction of the 5,6-double bond. On the contrary, in an acidic medium like CF₃COOH, the 5,6-double bond is reduced first (kinetically-controlled reaction). The dihydro-intermediate then undergoes a [1,2]-H-rearrangement leading to the formation of the thermodynamically more stable 7-methyl-7,8-dihydropterin (XV) which on further reduction gives 7-methyl-5,6,7,8-tetrahydropterin (VIII). The catalytic reduction of 7-methyl-7,8-dihydropterin (XV) with deuterium gives stereoselectively a sole product with D at C(6) in the equatorial position.     

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. 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. 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. 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. 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 67. Mitteilung Zum Verlauf der katalytischen Reduktion von 6, 7-Diphenylpterin

On the pathway of the catalytic reduction of 6,7-diphenylpterin The pathway of the hydrogen addition to the pyrazine ring of 6, 7-diphenylpterin ( 1a ) during acid-catalyzed reduction was elucidated. Initial hydrogenation of the 5, 6-double bond produces 6, 7-diphenyl-5, 6-dihydropterin ( 2a ); this then undergoes a [1, 2]-H-rearrangement, which yields the thermodynamically more stable 6, 7-diphenyl-7, 8-dihydropterin ( 3a ). Subsequent reduction of 3a gives 4 .     

Über Pterinchemie. Mitteilung. Die Kristallstruktur von 5,6,7-Trimethyl-5,6,7,8-tetrahydropterindihydrochlorid-monohydrat

The crystal structure of 5,6,7-trimethyl-5,6,7,8-tetrahydropterine-dihydrochloride-monohydrate The crystal structure of the title compound has been determined by X-ray analysis (direct methods) and refined with 947 structure amplitudes to R = 0.026. The crystal system is orthorhombic, space group Pna2₁, with unit cell dimensions a = 14.081, b = 14.623, c = 6.773 Å. The molecule is protonated at the N(1)- and N(5)-position. The tetrahydropyrazine ring exists in a conformation in which C(6) deviates markedly from the mean plane of the other five atoms. The CH₃-groups at N(5) and C(6) possess a trans configuration with a pseudoaxial and an axial conformation respectively. The CH₃-groups at C(6) and C(7) in return possess the cis configuration, whereby the CH₃-group at C(7) occupies an equatorial conformation.     

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 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. 60. vorläufige Mitteilung [1]. Eine neue,regiospezifische Synthese von L-Biopterin

A new, regiospecific synthesis of L -biopterine Pure L -biopterine (I) is obtained in 35–40% yield by condensation of 5-desoxy-L -arabinose-hydrazone acetate with 2,4,5-triamino-6-hydroxy-pyrimidine, followed by oxidation of the formed tetrahydro-derivative and deacetylation of the L -bioterine diacetate. Catalytic reduction of the L -biopterine gives the expected mixture of two diastereomeric tetrahydro-L -biopterines.