Crane Christine M, Boger Dale L
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
J Med Chem. 2009 Mar 12;52(5):1471-6. doi: 10.1021/jm801549b.
The synthesis and biological evaluation of a series of vancomycin aglycon analogues bearing alternative residue 1 N-methyl-D-amino acids are described. The analogues were prepared to define whether H-bonding d-amino acids could improve the affinity for the model ligands N,N'-Ac(2)-L-Lys-D-Ala-D-Ala (2) and N,N'-Ac(2)-L-Lys-D-Ala-D-Lac (3) and improve antimicrobial activity against vancomycin-sensitive or vancomycin-resistant bacteria. Additionally, a series of analogues with appended nucleophiles (hydrazines and amines) on the residue 1 D-amino acids are described that were examined for their ability to react with the C-terminal ester of 3, forming a covalent attachment of L-Lys-D-Ala to the natural product analogues.
本文描述了一系列带有替代残基1 N-甲基-D-氨基酸的万古霉素苷元类似物的合成及生物学评价。制备这些类似物是为了确定氢键供体D-氨基酸是否能提高对模型配体N,N'-二乙酰-L-赖氨酸-D-丙氨酸-D-丙氨酸（2）和N,N'-二乙酰-L-赖氨酸-D-丙氨酸-D-乳酸（3）的亲和力，并提高对万古霉素敏感或耐药细菌的抗菌活性。此外，还描述了一系列在残基1 D-氨基酸上带有亲核试剂（肼和胺）的类似物，研究了它们与3的C-末端酯反应的能力，从而使L-赖氨酸-D-丙氨酸与天然产物类似物形成共价连接。
