Corrins metallation

Carboxy derivatives of seco-corrin metal complexes can be synthesized as shown in Scheme 17. Using the nickel(II) complex (86), treatment with acetic acid/triethylamine in toluene at 110° gave a 56% yield of the nickel corrin (87), along with about 20% of the decarboxylated uncyclized material (88). This latter observation suggested that the ring closure step precedes decarboxylation in accord with this it was shown that the intermediate nickel 19-carboxy-... 

The macro-ring system of four partially reduced pyrrole nuclei joined through three bridge-carbon atoms is designated corrin, metal derivatives of this compound are designated cobalto-corrin, cohalti-corrin, etc. 

The structure of the diamagnetic, cherry-red vitamin B12 is shown in Fig. 26.6 and it can be seen that the coordination sphere of the cobalt has many similarities with that of iron in haem (see Fig. 25.7). In both cases the metal is coordinated to 4 nitrogen atoms of an unsaturated macrocycle (in this case part of a corrin ring which is less symmetrical and not so unsaturated as the porphyrin in haem) with an imidazole nitrogen in the fifth position. A major... 

Scheme 1 outlines the retrosynthetic analysis of the Woodward-Eschenmoser A-B variant of the vitamin B12 (1) synthesis. The analysis begins with cobyric acid (4) because it was demonstrated in 1960 that this compound can be smoothly converted to vitamin B12.5 In two exploratory corrin model syntheses to both approaches to the synthesis of cobyric acid,6 the ability of secocorrinoid structures (e. g. 5) to bind metal atoms was found to be central to the success of the macrocyclization reaction to give intact corrinoid structures. In the Woodward-Eschenmoser synthesis of cobyric acid, the cobalt atom situated in the center of intermediate 5 organizes the structure of the secocorrin, and promotes the cyclization... 

Vitamin B12 (Fig. 1) is defined as a group of cobalt-containing conoids known as cobalamins. The common features of the vitamers are a corrin ting (four reduced pyrrole rings) with cobalt as the central atom, a nucleotide-like compound and a variable ligand. Vitamin B12 is exceptional in as far as it is the only vitamin containing a metal-ion. The vitamers present in biological systems are hydroxo-, aquo-, methyl-, and 5 -deoxyadenosylcobalamin. 

The macrocycle types discussed so far tend to form very stable complexes with transition metal ions and, as mentioned previously, have properties which often resemble those of the naturally occurring porphyrins and corrins. The complexation behaviour of these macrocycles contrasts in a number of ways with that of the second major category of cyclic ligands - the crown polyethers. 

As a class, metal-ion derivatives of tetrapyrrole macrocyclic rings, such as the corrins or porphyrins (see Chapter 1 for the parent ring structures), are of major biological importance. 

Atom Transfer Atom Transfer (AT) takes place typically in the case of d7 complexes, which abstract the halogen atom from RX. The radical formed combines then with a second metal [193, 194]. A classical example of this mechanism is the hydrodehalogenation with cyanocobaltates(II) (see Section 18.2.1) [8, 9], but an analogous pathway was suggested recently for the Co(II) corrin-catalyzed dechlorination of CC14 in the presence of S2 /cysteine as reductant (Eqs. (11)—(12))... 

The corrins and porphyrins are another important class of natural chelator molecules (Figure 2.4). They are thermodynamically very stable and have four nearly coplanar pyrrole rings, the nitrogen atoms of which can accommodate a number of different metal ions in different oxidation states like Fe2+ in haem, Mg2+ in chlorophyll and Co3+ in vitamin B12. 

As we will see in subsequent chapters, many metalloproteins have their metal centres located in organic cofactors (Lippard and Berg, 1994), such as the tetrapyrrole porphyrins and corrins, or in metal clusters, such as the Fe-S clusters in Fe-S proteins or the FeMo-cofactor of nitrogenase. Here we discuss briefly how metals are incorporated into porphyrins and corrins to form haem and other metallated tetrapyrroles, how Fe-S clusters are synthesized and how copper is inserted into superoxide dismutase. 

This particular function, and also others of the metal, are also beautifully utilized in the work on the chemical synthesis of corrins (Fig. 6.2). In the synthesis of 2, a metal, Co(ll), Ni(ll) or Pd(ll), is required to stabilize the precursor 1, which would otherwise be extremely labile configurationally and constitutionally. As added bonuses, the metal ion helps to activate the methylene carbon for its attack on the iminoester carbon, and also forces the four nitrogens into a planar conformation, thereby bringing the condensation centers of rings A and B close together. This is strikingly shown by X-ray structural determination of 1. With... 

Many of the properties of metal ions in aiding or discouraging reactions are beautifully illustrated in the work on the chemical synthesis of corrins. Thus, it is appropriate to conclude this chapter by a relevant quotation from Eschenmoser ... 

The role of transition metals in the chemical synthesis of corrins is more than just adding a touch of inorganic elegance to organic synthesis- leave elegance to tailors and cobblers , a physicist once said — it is a vital role in the sense that perhaps no synthetic corrin would as yet exist without recourse to metal templates. Beside the purely topological function of arranging the proximity of reaction centres, metal ions have served this purpose as follows ... 

Vitamin Bjj (8.50, cobalamin) is an extremely complex molecule consisting of a corrin ring system similar to heme. The central metal atom is cobalt, coordinated with a ribofuranosyl-dimethylbenzimidazole. Vitamin Bjj occurs in liver, but is also produced by many bacteria and is therefore obtained commercially by fermentation. The vitamin is a catalyst for the rearrangement of methylmalonyl-CoA to the succinyl derivative in the degradation of some amino acids and the oxidation of fatty acids with an odd number of carbon atoms. It is also necessary for the methylation of homocysteine to methionine. 

Let me put it to Professor Lehn that biology can do better than he can with small molecules. From uroporphyrin biology makes (1) copper porphyrins (turacin feathers), (2) heme (iron) porphyrins, (3) magnesium chlorins, (4) cobalt corrins (B12). These compounds are formed with very little confusion between metals and partners. I cannot give selectivity factors, but they are very big. How is this managed Is it not better than man can do Maximum size selectivity for anions is not yet understood as few anion-binding sites in biology are known. 

Both of the above approaches employed a metal ion as a template about which the corrin cyclization was performed, but the nickel or cobalt ions could not subsequently be removed. In order to obtain metal-free corrins, a new route was therefore devised (67AG865) which employed the novel principle of sulfide contraction (Scheme 22). Thus the sodium salt of the precorrin (284) (Scheme 23) was transformed into the thiolactam (285), and loose complexation with zinc(II) ions caused cyclization to give (286), which was treated with benzoyl peroxide and acid to give the ring-expanded compound (287). Contraction with TFA/DMF gave the corrins (288) and (289), and the major of these (289) was desulfurized with triphenylphosphine and acid to give (288). Finally, demetallation with TFA gave the required metal-free corrin (290), a source for a whole variety of metal derivatives. 

In an approach of the type employed by Stevens, the metal-free corrin nucleus can be constructed, as shown in Scheme 26, by stepwise progression in either a clockwise or an anti-clockwise manner depending upon the choice, the tris-isoxazoles (294) or (295) should be accessible. 

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