Structure and Reactivity of Xanthocorrinoids. Part II. Influence of the c‐acetic‐acid chain on the course of the hydroxylation of the corrin chromophore by oxygen in the presence of ascorbic acid

Abstract

Dedicated to Prof. AIberf Eschenmoser on the occasion of his 60th birthday (28.5.85) The yield of the main product from the reaction of heptamethyl dicyanocobyrinate with 0, in the presence of ascorbic acid has been optimised by systematic variation of the reaction conditions, and the structure of the obtained 'stable yellow corrinoid' has been established by X-ray analysis. From the relationship between the structures of analogous xanthocorrinoids obtained likewise from a series of dicyanocobyrinic-acid derivatives, which has been prepared by systematic modifications of the c-acetic-acid chain, and the functionality of the substituent at C(7). a reaction mechanism is suggested.Stable yellow corrinoids, also termed 'xanthocorrinoids' [2], are formed as by-products of most reactions of cyanocobalamin (vitamin B,,) and its derivatives, which proceed with change of the oxidation state of the complex-bonded Co ion [3b]. They are stable to air and to light, and show, as a common feature, absorption bands at about 460480 nm, a spectral range which is also characteristic for some yellow compounds formed on degradation of vitamin B,, by bacteria (e.g. Aerohucter uerogenes [4] and Pseudomonus rubescens . Moreover, metal-free yellow corrinoids have been obtained from the culture fiitrates of phototrophic bacteria as Rhodopsezidomonus sphueroides or Rh. cupsulufa, when grown in a medium deficient in Co [lo]. However, as the structures of the above mentioned xanthocorrinoids are, with one exception, unknown, it is questionable whether all of them belong to the same class of compounds.Among the different reactions, which lead to the formation of stable yellow corrinoids from vitamin-B,, derivatives (cf. Fig. I ) , we investigated first the formation of such pigments under the conditions of Udenfriend's reaction using heptamethyl Cox, Copdicyanocobyrinate (1) as a substrate. Now, after a series of experiments directed towards the elucidation of the mechanism of the formation of xanthocorrinoids using different dicyanocobyrinic-acid derivatives as substrates has been completed [ 1 11, the experimental ') Part I [I]. 2, ') 4,

Structure and reactivity of xanthocorrinoids. Part V. Formation of trans‐diol derivatives of 5,6‐dihydrocobyrinic acid from xanthocorrinoids under acidic conditions

“…Some years ago, Bonnett [2] suggested that coordination of H,O, to the Co-ion of cobyrinic-acid derivatives may be the first step of their transformation into xanthocorrinoids with the Udenfriend reagent (ascorbic acid and 0, in MeOH at pH 7.2) [3]. This mechanism is not only consistent with the observed stereoselectivity of the reaction, which takes place on the more accessible p-face of the Co-complex, but also with the experimental evidence accumulated in our laboratory during the investigation of the influence of the substituent present at C(7) on the structure of the reaction product [4]. Particularly revealing proved to be the reactions of hexamethyl dicyanocob(II1)yrinate c&lactone (la) and hexamethyl dicyanocob(1II)yrinate c,8-lactam (lb) with 0, in the presence of ascorbic acid.…”

“…It is obvious, that protonation of OH-C(6) in 3 (+ 8) and subsequent elimination of H,O should afford the same cationic intermediate 9 (see Scheme) which has been suggested by Bonnett [2] and us [4] [14] as the common precursor of all different types of xanthocorrinoids which are known until now. Under the conditions of the Udenfriend reaction (pH 7.2), addition of an OH-ion from the more accessible p-face of the corrin macrocycle may be the rate-determining step of the reaction, thus yielding a cis-diol, which can be isolated (see 3) in the case of l b or which serves as intermediate in the formation of spirolactone 2 in the case of l a .…”

“…However, a still open but fundamental question related to the mechanism of corrinoid c-lactone formation concerns the oxidation step necessary in order to explain nucleophilic attack on C (8). Since abstraction of a hydride ion [2] is not likely under the employed esterification conditions, 'formal' transitory reduction of the Co"' to a Co' complex seems to be more plausible [4]. In the present case, 'formal' means, that electron transfer from the corrinoid macrocycle to an axial hydrogen sulfate ligand on the Co-ion may take place, yielding a cobalt sulfonic acid complex 12 analogous to the known 'sulfitocobalamin' [ 161.…”

“…Further confirmation of the correct structure of 4 was obtained accidentally in the course of our attempts to correlate xanthocorrinoid 5, which was obtained some time ago by oxidation of cyanocob(II1)alamin with Udenfriend's reagent in the presence of Cu" ions [l 11, with xanthocorrinoid 6 whose structure has been established unequivocally by X-ray diffraction analysis [4]. Attempted esterification of 5 by reaction with 10 Yo H,SO,/ MeOH did not lead, however, to 6 but to a new xanthocorrinoid 7, which was isolated in 24% yield.…”

“…Actually, whereas a cis-5,6-diol3 could be isolated as a reaction product of the latter, l a yielded a spirolactone 2 instead of the diol corresponding to 3. These results were interpreted as a consequence of the fact, that lactams are, in general, less prone to nucleophilic cleavage than lactones [4]. Moreover, the low yield of 3 (ca.…”