Über Pterinchemie. 70. Mitteilung. Konformationsanalyse von 5, 10‐Methenyl‐(6 RS)‐5,6,7,8‐tetrahydro‐L‐folsäure,

Abstract

Conformational analysis of S,IO-methenyl-(6RS)-5,6,7, S-tetrahydro-~-folic acid2)Summary Conformational analysis of the diastereomeric 9,9-dideu~terio-5,10-methenyl-(6RS)-5,6,7,8-tetrahydro-~-folic acids (IV) in the lOO-MHz-'H-NMR. spectrum shows a trans-diaxial arrangement of Ha-C (6) (A -part) and Ha-C (7) (X-part) (.IAX= 10.6 Hz) and a gauche arrangement of Ha-C(6) and He-C(7) (M-part) (JAM= 4.2 Hz). Accordingly the tetrahydropyrazine ring in IV exists in the same manner as in tetrahydrofolic acid but with a more marked half chair conformation and with a pseudo equatorial position of the C (6), C (9) bond.A similar analysis of the diastereomeric 7,7-dideuterio-5,10-methenyl-(6RS)-5,6,7,8-tetrahydro-~-folic acids (VIII) in the 360-MHz-lH-NMR. spectrum shows an almost identical situation with higher values of S between Ha-C(6) (A-part) and H-C(9,6) (B-part) on one side ( J = 11.2) and between Ha-C(6) and H-C(9a) (X-part) on the other side ( J A X = 9.2). This can be reached only when the imidazolinium ring of VIII is nearly planar (Fig. 3). 1. Einleitung. -In Fortsetzung der Arbeiten iiber die Konfiguration von 7,8-Dihydro-[2] und 5,6,7,8-Tetrahydropterin-Derivaten [ 11 dehnen wir mit der vorliegenden Arbeit die Untersuchungen auf das Gemisch der diastereomeren 5,lO-Methenyl-(6RS)-5,6,7,8-tetrahydro-~-folsauren (IX) aus. Bekanntlich ist eines der beiden Diastereomeren IX eine Zwischenstufe sowohl fur die chemische wie fur die enzymatische fiberfiuhrung von 5bzw. lO-Forrnyl-5,6,7,8-tetrahydro-~-

5,10-Methenyl-5,6,7,8-tetrahydromethanopterin, a one-carbon carrier in the process of methanogenesis

“…Reported by Armarego & Waring (1980). 'Reported by Khalifa et al (1979). /A coupling with 31P was observed.…”

5-Formyl- and 10-formyl-5,6,7,8-tetrahydrofolate. Conformation of the tetrahydropyrazine ring and formyl group in solution

“…The minor form of 5-CHO-H4folate could not be separated from the major form by gel permeation chromatography on Sephadex G-25 or by a salt gradient elution from an ion-exchange column packed with DEAE-Sephadex A-25. The minor form had different chemical shifts for its resonances than did the degradation products seen when 5-CHO-H4folate was exposed to oxygen or light; the resonances of the minor form were also different from those of 10-CHO-H4foíate (see Table IV) and from 5,10-methenyl-5,6,7,8-tetrahydrofolate (Khalifa et al, 1979).…”

“…The chemical shift and spin-spin splittings of the resonances of 10-CHO-H4folate in 0.1 M sodium phosphate, pH* 6.79, are given in Table IV. The resonances corresponding to C-(2',6')-2H, C(3',5')-2H, -CH, y-CH2, /3-CHA, and /3-CHB were assigned as in 5,10-CH+-H4folate (Khalifa et al, 1979) and 5-CHO-H4folate (see Table I). The resonance of 8.57 ppm was assigned to the formyl hydrogen, C(11)-H, through the similarity of its chemical shift to those of model compounds (Burdick et al, 1977) and to the chemical shift of C(11)-H in 5-CHO-H4folate (see Table I) and 5,10-CH+-H4folate (Khalifa et al, 1979).…”

“…The resonances corresponding to C-(2',6')-2H, C(3',5')-2H, -CH, y-CH2, /3-CHA, and /3-CHB were assigned as in 5,10-CH+-H4folate (Khalifa et al, 1979) and 5-CHO-H4folate (see Table I). The resonance of 8.57 ppm was assigned to the formyl hydrogen, C(11)-H, through the similarity of its chemical shift to those of model compounds (Burdick et al, 1977) and to the chemical shift of C(11)-H in 5-CHO-H4folate (see Table I) and 5,10-CH+-H4folate (Khalifa et al, 1979). This resonance had an area corresponding to 0.4 ± 0.1 proton when standardized against the C(2,,6,)-2H and C(3,5')~2H resonances.…”

“…The crystal structures of both the natural and unnatural diastereomers of 5,10-CH+-H4folate have been recently solved by Fontecilla-Camps et al ( 1979), and the NMR spectrum of its diastereomeric mixture has been fully analyzed to measure its conformation in solution by Khalifa et al (1979). A partial NMR spectrum of 5-CHO-H4folate has previously been reported by Pastore (1967) but not fully analyzed.…”