Selected Vitamins - Natural Products Chemistry: Sources, Separations, and Structures - page 139

a key regulatory role in the normal working function of the brain and the nervous sys-
tem. In fact, high Vit B 12 levels in elderly individuals may protect against brain atrophy
or shrinkage associated with Alzheimer's disease and impaired cognitive function.
Vit B 12 plays a role in carbohydrate metabolism. Also, it has a role in the synthesis
of red blood cells. In the absence of Vit B 12 , there is no maturation, leading to abnor-
mally large red blood cells.
12.7.1 S truCture e luCidation of V itamin B 12
The elucidation of the entire structure of Vit B 12 can be described in stages of iden-
tifying several of the compound's building blocks and piecing them together. This
painstaking work was completed without the benefit of today's modern spectroscopic
tools. First, the D-1 aminopropan-2-ol structure was found by observing a phosphate
associated with a fluorescent substance that gave a ninhydrin reaction under acidic
or basic hydrolytic conditions.
The identity of a 5,6-dimethylbenziminazole was revealed after chromatographic
and spectroscopic studies of a hydrolyzed fragment. The sugar derivative was iso-
lated as a pentose (through consumption of one mole of periodate). The coordination
of the N atom of the 5,6-dimethylbenziminazole moiety to the cobalt metal was
shown by spectroscopic studies. The UV absorption maxima at 360 mu, 520 mu,
and 550 mu are characteristic of a corrinoid unit, whereas the absorption at 289 mu
corresponds to the 5,6 dimethylbenzimidazole substituent.
Researchers showed the complex macro ring structure to be a corrin, not porphy-
rin, by having a reduced ring structure and one of the meso bridges replaced by a
direct linkage. Eventually, the complete structure was confirmed by X-ray crystal-
lography in the 1950s.
The mass spectrum of Vit B 12 displays a molecular ion (M+H) + , m/z 1355.54. In
the NMR spectrum, some assignments were made from 1-dimensional 1 H NMR:
methyl (Pr3), and methane (C19H and R1H) multiplicity. Using selective decoupling
techniques with comparison to small compounds (axial nucleotide, adenosyl ligand)
and spectra of cobalamins with various beta axial ligands and protonation on the
benzimidazole-base comparisons, the structure was elucidated.
12.7.2 C ommerCial p roduCtion
Chemical synthesis requires more than 70 steps. Thus, the process is tedious, expen-
sive, and not amenable to large-scale production. Fortunately, fermentation processes
using bacteria produce cobalamin derivatives by similar pathways to a chemical syn-
thesis. The production is improved with additions of cobalt ions, glycine, threonine,
and choline into the fermentation medium. Upon completion of the fermentation step,
the filtered broth can be extracted using an organic solvent such as dichloromethane.
SUMMARY
Several vitamins are described to indicate the variety of the chemistry. They were
Vit C, Vit D, Vit E, Vit B 6 , and Vit B 12 .