Chavdarian C G, Castagnoli N
J Med Chem. 1979 Nov;22(11):1317-22. doi: 10.1021/jm00197a008.
In an attempt to further characterize the structural features of 6-hydroxydopamine analogues that are associated with in vivo neuronal degeneration, the synthesis of 6-mercaptodopamine was undertaken. Although reaction conditions leading to the 1,4 addition of thiols to the model quinone 4-methyl-o-benzoquinone were achieved, attempts to obtain 6-thiolated dopamine analogues by this route failed. The synthesis of 6-mercaptodopamine was achieved by the regioselective thiocyanation of O,O-dimethyldopamine, followed by bis-O-demethylation and reductive cleavage of the S-cyano group. Unlike 6-hydroxydopamine, 6-mercaptodopamine was resistant to autoxidation at pH 7.4. Cyclic voltammometric analysis, however, indicated that electrochemically generated oxidation species of 6-mercaptodopamine are unstable and undergo spontaneous reaction, presumably intramolecular cyclization. In vivo tests revealed that 6-mercaptodopamine inhibits the uptake of tritium-labeled norepinephrine by isolated rat heart atria, although to a much lesser extent than 6-hydroxydopamine.
为了进一步表征与体内神经元变性相关的6-羟基多巴胺类似物的结构特征，开展了6-巯基多巴胺的合成研究。尽管实现了硫醇对模型醌4-甲基邻苯醌进行1,4-加成的反应条件，但通过该途径获得6-硫醇化多巴胺类似物的尝试却失败了。6-巯基多巴胺的合成是通过对O,O-二甲基多巴胺进行区域选择性硫氰化，然后进行双-O-去甲基化和S-氰基的还原裂解来实现的。与6-羟基多巴胺不同，6-巯基多巴胺在pH 7.4时抗自氧化。然而，循环伏安分析表明，6-巯基多巴胺的电化学生成氧化物种不稳定，并会发生自发反应，推测是分子内环化反应。体内试验表明，6-巯基多巴胺会抑制离体大鼠心房对氚标记去甲肾上腺素的摄取，尽管其抑制程度远低于6-羟基多巴胺。
