785. A partial synthesis of the vitamin B12 coenzyme and some of its analogues

Abstract

The vitamin B,, coenzyme has been partially synthesised from hydroxocobalamin (vitamin Blzb) by reduction followed by reaction with a 5'-tosyladenosine. Many analogues, including simple alkyl and acyl derivatives, have been obtained by similar methods. The reactive intermediate is postulated as a cobalt hydride on the basis of its addition to a variety of ethylenic and acetylenic compounds, yielding further analogues of the coenzyme. Reaction of the cobalt hydride with diazomethane gives the cobalt-methyl derivative. Certain reactions of the products are described.THE vitamin B,, coenzymes were first isolated by Barker and his colleagues,l and the chemical structure (I) of one of them, the 5,6-dimethylbenzimidazolylcobamide coenzyme was established by X-ray crystallographic and chemical analysis., The other coenzymes of the group differ only in the nature of the base contained in the nucleotide fragment. The novel cobalt-carbon bond linking the metal to the 5'-deoxyadenosine group of the coenzyme (I ; R = 5'-deoxyadenosyl) is easily broken by a variety of chemical reagents as well as by light, and many transformation products of the coenzyme have been characterised (see, e.g., refs. 3 and 4). Apart from the possible addition of hydrogen at C,-C,, in the corrin nucleus * the main ambiguity of structure (I; R = 5'-deoxyadenosyl) concerns the cobalt atom, which is probably tervalent on the basis of the observed chemical reactions, although there have been claims that the coenzyme is paramagnetic, which would suggest the presence of bivalent cobalt.* Until this ambiguity is resolved, the " cobalamin " nomenclature for the coenzymes and their analogues (I), e.g., " methylcobalamin " for (I; R = Me), has been avoided:

Synthesis and Properties of Formylcobalamin and Propionylcobalamin, Novel Acylcobalamins

“…Some properties, especially the stability of the Co-C bond, of this novel acylcobalamin (acyl-Cbl) are also described here, compared with those of propionylcobalamin (propionyl-Cbl), another novel acyl-Cbl, and acetylcobalamin (acetyl-Cbl). The synthesis (8)(9)(10) and some properties (8,10,11) of acetyl-Cbl were reported earlier by other investigators.…”

“…J Nutr Sci Vitaminol, 61, [8][9][10][11][12][13]2015 Cobamide coenzymes including adenosylcobalamin (AdoCbl) are naturally occurring organometallic compounds that contain a unique cobalt-carbon (Co-C) -bond ( Fig. 1) (1)(2)(3)(4).…”

Cob(I)alamin as Catalyst. 8th Communication. Cob(I)alamin and Heptamethyl Cob(I)yrinate During the Reduction of α,β‐Unsaturated Carbonyl Derivatives

“…The product was shown to be the corresponding saturated ester 3 with (S)-configuration at the chiral center showing enantiomeric excesses of 16.2-23.8% depending on the reaction conditions applied. The formation of alkylcobalamins by a nucleophilic attack of cob (1)alamin on a,P-unsaturated carbonyl derivatives is well documented in the literature [4] [5]. It is therefore reasonable to expect intermediate alkylcobalamins during this overall reduction of a double bond.…”

Cob(I)alamin als Katalysator. 6. Mitteilung [1]. Bildung und Fragmentierung von Alkylcobalaminen, ein Gleichgewichtsprozess zwischen nukleophiler Addition und reduktiver Fragmentierung

“…-Alkylcobalamine, gut bekannte organometallische Verbindungen, die auch in der Natur in Form von Methylcobalamin [2] [3] und Coenzym BI2 [4] vertreten sind, werden oft durch Angriff des stark nukleophilen [5] @-Cob-(1)alamins') an elektrophilen C-Zentren hergestellt [5] [ 1 1-13]*). Reaktionsmechanistisch sind Sub~titutionen~) von Abgangsgruppen [ 121 [16][17][18][19][20][21][22][23][24], Elektronen-Transfer-Reaktionen [ 121 [25] [26], Anlagerungen an die Doppelbindung von Acrylsystemen [2 11 [27], Offnung von Epoxiden, Athylenimin und Tetrahydrofuran [2 11 [22] [28] [29] sowie Anlagerungen an isolierte Dreifachbindungen [2 11 mehrfach beschrieben. Wenig hingegen wurde uber die Addition an isolierte Doppelbindungen veroffentlicht.…”