The Chemistry of Anti-Pernicious Anaemia Factors

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Abstract
Summary and Conclusions: Evidence is presented for the presence of three chemically related substances, components α, β, and γ, in acid hydrolysates of vitamin B12. Spectroscopic examination of these components has led to their classification as benziminazole derivatives. Spectroscopic comparison with 22 methylated benziminazoles synthesised to serve as model compounds, has resulted in the identification of components α and β as 1:5:6-trisubstituted benziminazoles, and of component γ as a 5:6-disubstituted benziminazole. Preliminary paper chromatographic studies point to the identity of component γ with 5:6-dimethylbenziminazole; from which it is concluded that components α and β are both 1-substituted 5:6-dimethyl-benziminazoles. Spectroscopic and chemical evidence leads to the conclusion that only one 5:6-dimethylbenziminazole residue is released from vitamin B12 on acid hydrolysis and that the benziminazole nucleus exists preformed in the vitamin. It is, therefore, concluded that components α, β, and γ represent successive stages of degradation of a common precursor. The bearing of these results on the biogenesis and structure of vitamin B12 is briefly discussed. It is a pleasure to acknowledge the encouragement of the Directors of The British Drug Houses, Ltd., in this work. Footnote. While preparing this paper for publication we became aware at the meeting of the First International Congress of Biochemistry held at Cambridge in August, 1949, of the findings of Dr. K. Folkers and his colleagues, and at the same session we announced the conclusions we had reached in the work now reported (Holiday and Petrow, J. Pharm. Pharmacol, 1949, 1, 734).