Vitamin B12

Vitamin B12 is the nutritional factor required for the prevention of pernicious anemia. Its structure was determined in 1956 through the chemical studies of Alexander Todd (Nobel Prize, 1957) and the x-ray diffraction studies of Dorothy Hodgkin (Nobel Prize, 1964). It is one of the most complex natural products known, yet it has features that are not unfamiliar. It is related to the metalloporphyrins discussed previously, but the ring system surrounding the cobalt atom has one less carbon bridging two of the nitrogen-containing rings than the porphyrin ring of heme or chlorophyll. The B12 ring system is called a corrin ring, and the vitamin is a cobalt-corrin complex.

The corrin ring includes methyl, ethanamide, and propanamide groups, and one of these is linked through a nucleotide residue to the cobalt atom. There are five nitrogen ligands around the cobalt, and a sixth ligand is attached through carbon - here a cyano group - so that an alternate name for vitamin B12 is cyanocobalamin:

A total synthesis of vitamin B12 was announced in 1972, as the result of a collaborative effort between R. B. Woodward (Harvard) and A. Eschenmoser (Zurich). The synthesis was completed after 11 years of effort involving 100 co-workers from 19 countries. A number of important techniques and reactions of synthetic value were developed during the course of this work, including the principle of conservation of orbital symmetry.