Cobyrinic acid, 259: synthesis

Scheme 20. Synthesis of cobyrinic acid abcdeg hexamethylester f nitrile 96.

Scheme 21 presents the successful sequence of reactions that solved the remaining two problems and led to the completion of the synthesis of cobyric acid. Exposure of 96 to concentrated sulfuric acid for one hour brings about a clean conversion of the nitrile grouping to the corresponding primary amide grouping. The stability of die corrin nucleus under these rather severe conditions is noteworthy. This new substance, intermediate 97, is identified as cobyrinic acid abcdeg hexamethylester f amide and it is produced along with a very similar substance which is epimeric to 97 at C-13. The action of sulfuric acid on 96 produces a diastereomeric... 

Cobyrinic acid acts as the substrate for the first of two amidases, CbiA, which amidates the a and c acetic acid side chains (Figure 24). As with CobB, CbiA uses glutamine as its preferred amino donor and requires ATP as an energy source. Kinetic analysis has shown that the hydrolysis of glutamine and the synthesis of cobyrinic acid tf,c-diamide are uncoupled. It was also shown that the amino groups are transferred in the order of r first and then a, allowing a model to be proposed whereby phosphinylated intermediates are formed. ... 

Synthesis of uroporphyrinogen III from 6-ALA via porphobilinogen. - 2) C-Methylation of uroporphyrinogen III by a series of different methyltransferases with use of S-adenosylmethionine (SAM), decarboxylation, ring contraction, and incorporation of cobalt with formation of cobyrinic acid, the simplest representative of the naturally occurring corrins. - 3) Conversion of cobyrinic acid to cobalamin and then to the coenzyme form of V. B 2. 

The completely amidated cobyrinic acid without isopropanol residues is called cobyric acid. Cobyric acid containing isopropanol is named cobinic acid, and its amide, cobinamide. L-threonine is the precursor for l-amino-2-propanol (Ford and Friedman, 1976). The complete corrinoids contain DMB as the lower (Co-a) nucleotide ligand. In anaerobic producers of corrinoids the synthesis of DMB differs from its aerobic synthesis. Aerobic and aerotolerant microorganisms form this base from FMN. Propionibacteria can use different forms of flavins riboflavin, FMN and FAD as precursors of the vitamin B nucleotide ligand (Jaszewski et al., 1995). 

Illumination of suspensions of P. shermanii by light (2000-2500 lux) for 48-72 h sharply decreases the production of vitamin B and its corrinoid precursors, cobyrinic acid and its amides, and is accompanied by a considerable increase in porphyrin synthesis (mainly coproporphyrins III) (Yeliseev and Bykhovsky, 1990). The amidation of cobyrinic acids is an important regulatory step of the vitamin Bn biosynthesis (Yeliseev et al., 1988). When methylation is impaired, polycarboxylic corrinoids accumulate, inhibiting steps that precede the synthesis of corrinoids, including the methylation of UPB III (Bykhovsky and Zaitseva, 1989). 

---