Quantitative Determination of Dihydrostreptomycin by Periodate Oxidation.

Dihydrostreptomycin is produced commercially by the catalytic hydrogenation of streptomycin. The reaction involves the reduction of the aldehyde group in the streptose moiety of the streptomycin molecule to the corresponding primary carbinol group as evidenced by the failure of dihydrostreptomycin to react with carbonyl reagents or with alkali to produce maltol. As there are no chemical methods available for the direct determination of dihydrostreptomycin, it was desirable to investigate the development of such a method. A satisfactory procedure has been found and is based upon the measurement of formaldehyde liberated by the periodate oxidation of dihydrostreptomycin. Periodate oxidation is a general method of cleaving the linkage between two adjacent hydroxyl bearing carbon atoms. If one of the hydroxyl groups is a primary carbinol, formaldehyde will be a reaction product (1). In the elucidation of the structure of streptomycin, it has been proven there is no primary carbinol group which will give rise to formaldehyde on treatment with periodate (2, 3). However, in the case of dihydrostreptomycin there is a primary carbinol adjacent to an hydroxyl, and formaldehyde is liberated by periodate oxidation. This has been observed experimentally by Lemieux, DeWalt and Wolfrom (4). These workers showed that dihydrostreptomycin when oxidized with 1.5 mole of periodate yielded 0.5 mole of formaldehyde while streptomycin yielded no formaldehyde. Fried and Stavely (5) have also found that the action of periodic acid on streptomycin B and on dihydrostreptomycin B produces zero and one mole of formaldehyde, respectively. Sodium metaperiodate was found to be the most suitable reagent for the oxidation of dihydrostreptomycin. Although the action of the salt