Liu Yuan, Jacobs Hollie K, Gopalan Aravamudan S
Department of Chemistry and Biochemistry, MSC 3C, New Mexico State University, Las Cruces, New Mexico 88003-8001, USA.
J Org Chem. 2009 Jan 16;74(2):782-8. doi: 10.1021/jo802410u.
Hydroxamic acids are an important class of chelators of hard metal ions such as Fe(III), which have found applications in therapeutic, diagnostic, and separation chemistry. Hence, methods for their preparation and incorporation into various matrices are important. A new strategy for the preparation of hydroxamic acids that uses readily available N-benzyloxy carbamic acid ethyl ester, 1, has been developed. N-Alkylation of 1 occurs readily to give N-alkyl-N-benzyloxy carbamates, 2, which react with a variety of stabilized carbon nucleophiles to give functionalized protected hydroxamic acids, 3, in good to excellent yields. The O-protected hydroxamate intermediates 3 can be further alkylated with halides to access a variety of potential metal binding hosts. The usefulness of this methodology has been demonstrated by the synthesis of a novel trihydroxamic acid 6, mixed ligand systems 9 and 12, and the macrocyclic dihydroxamic acid 16.
异羟肟酸是一类重要的硬金属离子螯合剂，如Fe(III)，已在治疗、诊断和分离化学中得到应用。因此，其制备方法以及将其引入各种基质的方法都很重要。已经开发出一种制备异羟肟酸的新策略，该策略使用易于获得的N-苄氧基氨基甲酸乙酯1。1易于进行N-烷基化反应生成N-烷基-N-苄氧基氨基甲酸酯2，2与各种稳定的碳亲核试剂反应，以良好至优异的产率生成官能化的受保护异羟肟酸3。O-保护的异羟肟酸酯中间体3可以进一步用卤化物进行烷基化反应，以获得各种潜在的金属结合主体。通过合成新型三异羟肟酸6、混合配体体系9和12以及大环二异羟肟酸16，证明了该方法的实用性。
