The major diseases of iron metabolism are iron deficiency anaemia, which could be treated using Fe2+ or Fe3+ salt supplements, and iron overload, which could arise either from an increased gastrointestinal absorption of iron or from recurrent blood transfusions. While the former form of iron overload could be treated by phlebotomy the latter requires the use of a chelator. Desferrioxamine is the only clinically available chelator for the treatment of iron overload but its use worldwide is limited because it is expensive and orally inactive. Several alpha-ketohydroxy heteroaromatic chelators have been synthesised and tested for their iron binding properties at physiological pH. The synthetic route involves the benzylation of the hydroxyl group of maltol using benzyl chloride, the conversion of the benzylated maltol to the 1-alkyl benzylated pyridine derivative by introducing the corresponding alkylamine in alkaline conditions and the cleavage of the benzyl group in acid to form the 1-alkyl-2-methyl-3-hydroxypyrid-4-one. All the chelators are water soluble and stable at a wide range of pH, forming stable, water soluble, coloured iron complexes with a molar ratio of approximately 3 chelator: 1 iron at pH 7.4 and lower molar ratio of chelators to iron complexes at acidic pH. When the 1-methyl, 1-ethyl and 1-propyl, -2-methyl-3-hydroxypyrid-4-ones were mixed at pH 7.4 with transferrin, ferritin and haemosiderin substantial amounts of iron were released.(ABSTRACT TRUNCATED AT 250 WORDS)

中文翻译：

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1-烷基-2-甲基-3-羟基吡啶-4-酮的新合成方法和铁螯合研究。

铁代谢的主要疾病是缺铁性贫血，可使用Fe2 +或Fe3 +盐补充剂治疗；铁超负荷，可能是由于胃肠道对铁的吸收增加或输血反复引起的。前一种形式的铁超负荷可以通过放血来治疗，而后者则需要使用螯合剂。去铁胺是唯一可用于治疗铁超负荷的临床螯合剂，但由于其价格昂贵且无口服活性，因此在全球范围内的使用受到限制。已经合成了几种α-酮羟基杂芳族螯合剂，并在生理pH下测试了它们的铁结合性能。合成途径涉及使用苄基氯将麦芽酚的羟基苄基化，通过在碱性条件下引入相应的烷基胺并将苄基在酸中裂解形成1-烷基-2-甲基-3-羟基吡啶-4-酮，将苄基麦芽酚转化为1-烷基苄基吡啶衍生物。所有螯合剂都是水溶性的，并且在很宽的pH范围内都是稳定的，形成稳定的，水溶性的有色铁络合物，摩尔比约为3螯合剂：pH 7.4时为1铁，而在酸性pH值下螯合剂与铁络合物的摩尔比较低。当在pH 7.4下将1-甲基，1-乙基和1-丙基，-2-甲基-3-羟基吡啶-4-酮与转铁蛋白，铁蛋白和血铁蛋白混合时，会释放出大量的铁（摘要以250字截断） ）有色铁配合物，其摩尔比约为3：螯合剂：pH 7.4时为1的铁，在酸性pH值下螯合剂与铁配合物的摩尔比较低。当在pH 7.4下将1-甲基，1-乙基和1-丙基，-2-甲基-3-羟基吡啶-4-酮与转铁蛋白，铁蛋白和血铁蛋白混合时，会释放出大量的铁（摘要以250字截断） ）有色铁配合物，其摩尔比约为3：螯合剂：pH 7.4时为1的铁，在酸性pH值下螯合剂与铁配合物的摩尔比较低。当在pH 7.4下将1-甲基，1-乙基和1-丙基，-2-甲基-3-羟基吡啶-4-酮与转铁蛋白，铁蛋白和血铁蛋白混合时，会释放出大量的铁（摘要以250字截断） ）