摘要：

Systematic investigations in the series of bisquaternary salts of 3,12-diaza-6,9-diazoniadispiro[5,2,5,2]hexadecane led to creation of the original antitumor drugs prospidin [1] and spirobromin [2]. These preparations differ from most known antitumor drugs by their low toxicity and virtually complete absence of depression of hemopoietic function. In continuation of the search for new antitumor drugs among structural analogs of the aforementioned compounds, we have synthesized a series of bisquaternary salts of 3,12-diaza-6,9-diazoniadispiro[5,2,5,3]heptadecane. This system was constructed using the reaction of cycloquaternization of 1,3-di(4-benzoylpiperazin-1-yl)propane (I) with 1,2-dibromoethane, which led to dibromide II with a yield of 70%. Boiling this compound in a 10% HBr solution leads to the hydrolysis of N-benzoyl groups with the formation of a bisquaternary salt III with a yield of 98%. By reacting salt III with the corresponding calculated amount of LiOH in an aqueous solution, we obtained bisquaternary compound IV with a yield of 75 – 78%. Note that the presence of excess LiOH leads to destructive changes in the dispiro system, which hinders the formation of dibromide IV. The use of LiOH (rather than other alkali metal hydroxides) for binding HBr in this reaction (similar to the synthesis of analogous dispirotripiperazinium derivatives [2]) is explained by the better solubility of lithium bromide (as compared to sodium and potassium bromides) in methanol. This circumstance is important from the standpoint of purification of dibromide IV, which is almost insoluble in organic solvents but well soluble in water. It was found that individual compound IV could be obtained only by repeated precipitation from concentrated aqueous solutions with methanol, ethanol, or acetone. In order to elucidate the character of transformations of

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