Tetrapyrrolic precursor

Porphyrinogens are cyclic tetrapyrrole precursors which give rise to three basic groups of molecules, discriminated by their state of oxidation porphyrins, dihydroporphyrins and tetrahydroporphryins the basic structures are depicted in Figure 2.1.1. 

It is necessary to devote a specific section to the nomenclature of corrinoids and of their linear tetrapyrrolic precursors because of the confusion existing in the literature about the correct naming of these compounds. 

Two major strategies have been considered in order to obtain metallocorrolates the first one consists of the reaction of the preformed macrocycle with metal ions, while the second involves the oxidative, base induced cycliz-ation of the open-chain tetrapyrrolic precursor dihydrobilin (1,19-dideoxybiladiene-a,c) in buffered alcoholic solution in the presence of metal salts. By proper tuning of the experimental conditions (reaction time, solvent, metal carrier) several metal complexes have been obtained and characterized. 

The 10-substituted complex has been prepared following the procedure outlined in Sect. 3.2. i.e. reacting the appropriate tetrapyrrolic precursor, 2,3,7,8,12,13,17,18-octamethyl-10-phenyl-dihydrobilin, with cobalt acetate in methanol. As in the case of the meso-unsubstituted complex, the presence of triphenylphosphine is reported to be essential for the isolation of the product. 

Figure 8-14. The copper-mediated formation of a porphyrin from a tetrapyrrole precursor.

The first [26]hexaphyrin(1.1.0.1.1.0) 154 (Scheme 63) was obtained by condensing tetrapyrrolic precursor 153 with the diformyl bipyrrole 124 under acid-catalyzed conditions, followed by air oxidation. The resulting macrocycle was assigned the trivial name "rubyrin" due to its dark orange-red color in DCM (1991ACI977). 

In 1992 the X-ray crystal structure of porphobilinogen deaminase was solved, an enzyme that is involved with the biosynthesis of a linear tetrapyrrole precursor to protoporphyrin IX, found in haemoglobin... 

The Falk procedure (Scheme 3.2.2), in contrast to the Sessler-Vogel one, relies on an Ullmann-type reaction using a dibromo or diiodo tetrapyrrolic precursor (e.g., 3.138-3.141) in its key, macrocycle-forming step. In accord with this general strategy, these workers found that heating the dibromo tetrapyrrole 3.138, or the... 

As implied above, the first synthesis of a sapphyrin was purely accidental and came about as the result of the reaction of the linear tetrapyrrolic precursor 5.1 with formic acid and HBr. Following oxidation with iodine, instead of obtaining the desired tetrapyrrolic corrole macrocycle, a different macrocycle was obtained (Scheme 5.1.1). This unexpected by-product was best formulated as being the deca-alkyl-substituted aromatic pentapyrrolic macrocycle 5.2. The unexpected formation... 

A sequence of an ozonolysis-PK reaction has been used to convert functionalized cyclohexenes to pyrroles (for example 49 and 50) that are important precursors to natural tetrapyrroles, hemes, and porphyrins ... 

The biosynthesis of the tetrapyrrole macrocycle and its branches leading to haem and chlorophylls has been covered in detail in several reviews - - and will be concisely described in this section. Tetrapyrrole biosynthesis occurs entirely in the plastids and is composed of several enzymatic steps starting from 5-aminolevulinic acid (ALA), which is the key precursor of porphyrins and the source of their carbon and nitrogen. 

In terms of synthetic strategy, approaches to porphyrins from open-chain tetrapyrroles are the only truly general routes. The principle is to construct, in a stepwise manner, an open-chain tetrapyrrole bearing a pre-determined arrangement of peripheral substituents. Cyclization to produce a porphyrin, or an immediate precursor, under mild conditions which do not cause redistribution of the pyrrole rings, should be accomplished after full characterization of the open-chain intermediate. 

When we consider a proper linear precursor for a corrin, which is a highly reduced structure, a different parent tetrapyrrole may be used this is named secocorrin and its shown in Fig. 5. 

This section will not be concerned with the detailed description of the synthetic methods leading to the appropriate precursors we will limit our attention to the crucial step of the synthesis of corrinoids, i.e. the formation of the tetrapyrrolic ring. The corrinoid macrocycle has been synthesized following two different procedures the first one involves the cyclization of a proper linear precursor, while the second involves ring contraction of a porphyrinoid structure. 

The synthetic pathways leading to tetradehydrocorrins and isobacteriochlorins are very similar and it is just by fine variations of the reaction conditions that the preparation is driven towards specific tetrapyrrolic rings. The linear precursors have been synthesized using the sulfide contraction method (also indicated by other authors as sulfur extrusion ). The corrin skeleton is formed by alkaline hydrolysis of the cyano protecting group present at the 19 position and subsequent acid catalyzed coupling of pyrroles A and D, as described in Fig. 26. 

On the contrary, neutral dithiaporphycene 207 (Scheme 84), with two thiophene units opposing each other could be obtained as a planar aromatic system much like the parent tetrapyrrolic porphycene 38. Oxidation of precursor 206 proceeded easily (1993T6863). 

Although the corrin nucleus of vitamin Bl2 (1) contains nine asymmetric carbon atoms, it is constructed by nature from achiral building blocks, and the first macrocyclic intermediate in the biosynthetic pathway, uroporphyrinogen III (60), is also achiral. Since uroporphyrinogen III is a common precursor of all tetrapyrrolic macrocycles, it is convenient to discuss its biosynthesis first and then summarize the known facts of the transformation of uroporphyrinogen III to the corrin nucleus. 

---