Komplementär diastereoselektive Cobalt‐Methylierungen des Vitamin‐B₁₂‐Derivates «Cobester»

Abstract

Treatment of heptamethyl cob(1)yrinate (2) in toluene/tetrahydrofurane (ca. 4 : 1) with methyl p-toluenesulfonate under exclusion of 0, and with protection from light leads to the selective formation of the heptamethyl Cop-methylcob(I1I)yrinate (perchlorate lb) in 75% yield. In contrast, methylation of 2 with methyl iodide under the same conditions results in the isomeric heptamethyl Coa -methylcob(III)yrinate (perchlorate la) in 73 % yield, besides 7 YO of 1 b. This complementary diastereofaceselectivity of the methylation at the Co-center results from alkylation under kinetic control and apparently involves two mechanistically distinct alkylation processes. A radical mechanism is considered to account for the stereochemically unusual outcome of the reaction with methyl iodide.Soweit bekannt, ist die bei der Reaktion der sogenannt ccsupernukleophilen)) [I] Cob(1)yrinsiiurederivate mit Alkylhalogeniden oder (primaren) Alkyltosylaten resultierende, der Struktur des Coenzyms B,Z [2] analoge 8-Konfiguration der Co-gebundenen Alkylgruppe in <(komplettenn Alkylcob(II1)yrinaten sowohl auf kinetische als auch auf thennodynamische Faktoren zuruckzufuhren, einschliesslich der dann moglichen Co-Koordination der Nukleotidbase von der a -Seite her [3]'). Ahnlich durfte eine thermodynamisch bedingte Praferenz fur die matiirlichei) (d. h. B-stiindige) Alkylgruppenkonfiguration ebenfalls fur die ctinkompletten)) Alkylcob(II1)yrinsiiurederivate vorliegen, denen der dirigierende Einfluss der a -standigen Nukleotidfunktion fehlt [3]. Jedenfalls uberwiegt nach einer von Friedrich et al. durchgefiihrten stereochemischen Korrelation*) bei mehreren, in wasseriger Losung thermo-und photolytisch aquilibrierten Methylcob(II1)yrinsaurederivaten das Koordinationsisomere mit Cop-Methyl-Konfiguration deutlich [6]. Die Moglichkeit, dass die Konfiguration am Metal1 (Cop us. Coa) durch mechanistische Faktoren der Alkylierung beeinflusst wird, scheint hingegen noch unbeachtet geblieben zu sein. ') Z. B. entsteht Cop-Athylcob(II1)alamin aus Cob(1)alamin und p-Toluolsulfonsaure-athylester in einer (auch) am Athyl-C-Atom (weitgehend) stereospezifischen Reaktion [4]. In H20 aquilibriertes Methylcob-(1II)aIamin liegt zu > 97% in der Cu~-Methyl-Konfiguration vor [5]. UVjVlS-und CD-spektroskopische Korrelation rnit Cop-und Coa-Methylcob(lIl)alamin 15-71. ')

Diversity of corrinoids in acetogenic bacteria

“…It is of interest that cobamide bioassays give varying responses according to the different cobamide types tested [l]. In addition, the kinetics of (de)methylations of cobalt corrins [35] and methyl transfer equilibria between corrinoid cobalt complexes [36] in aqueous solutions indicate that the nucleotide coordination in complete corrins affects the strenght of the cobalt-carbon bond in methyl corrinoids [37] as well as their electron transfer reactivity [37, 381. Further experiments with these cobamides are needed to test the particular situation of their biosynthesis, their biologically active corrinoid forms and their reaction specificity.…”

Coα-(1H-Imidazolyl)-Coβ-methylcob(III)amide: Model for Protein-Bound Corrinoid Cofactors

“…Within the first 2 h, the signals of the intermediate 12 (no formula shown) had grown to almost their maximal intensity, while those of 2 and 7 appeared more slowly, to reach by the end of the experiment (30 days) essentially the same solution composition as in reaction A. The position of two signals of the intermediate 12, a singlet at À 0.36 ppm (a high-field position typical of signals due to Co-bound Me groups) and a singlet at 0.95 ppm, would make it rather likely that 12 is a Coamethylcorrinoid in a base-off form [54]. Further experiments are planned to reveal the identity of 12.…”

Enhancing the Methyl-Donor Activity of Methylcobalamin by Covalent Attachment of DNA

“…The expected b-configuration of the axial, Cobound Me group, which gave rise to a singlet at À 0.18 ppm in the 1 H-NMR-spectrum of K 2 -5, was established with the help of a ROESY spectrum. It showed NOE crosspeaks to Me(12B) and Me(17B), the methylene groups CH 2 (21) and CH 2 (71), as well as to the characteristic methine doublet due to HÀC (19), all of which are situated on the b-face of the corrin ligand [45]. A signal at À 0.51 ppm (ca.…”