N-吡啶基对氯扁桃酰胺类化合物的合成

目的]N-吡啶基对氯扁桃酰胺类化合物及其衍生物具有良好的抗菌活性,部分化合物还可用于治疗青光眼、干眼等疾病。旨在探索合成N-吡啶基对氯扁桃酰胺类化合物的有效途径。方法]以对氯扁桃酸为原料,经乙酐保护羟基,羧基氯化、与氨基吡啶缩合,再经脱保护制得N-吡啶基对氯扁桃酰胺类化合物5a~5f,考察了各种氨基吡啶的反应活性和中间体4a~4f的脱保护条件。最后,通过菌丝生长速率法测试化合物5a~5f对番茄灰霉病菌的抑制率。结果]产品总收率达76%~84%,结构经1H NMR、IR谱确证。化合物5a~5f对番茄灰霉病菌的抑制率为17%~63%。结论]各种氨基吡啶都能与对氯扁桃酰氯有效缩合,化合物4a~4e都能在氢氧化钠/乙醇体系下脱保护,对碱较敏感的4f需在碳酸氢钠/乙醇体系下脱保护。该路线条件温和、收率高,为N-吡啶基对氯扁桃酰胺类化合物的合成提供了一种有效方法。活性测试表明化合物5a~5f具有一定的抗菌活性。

Synthesis of N-Pyridyl-p-chloro-mandelamide Derivatives

Aims] The N-pyridyl-p-chloro-mandelamides and their derivatives are proved to be of good antibacterial activity,some of these compounds can be used in the treatment of glaucoma and dry eye diseases.This paper is aimed at developing an effective way to synthesize the N-pyridyl-p-chloro-mandelamides.Methods] N-Pyridyl-p-chloro-mandelamides 5a-5f were prepared by protection of the hydroxy of p-chloro-mandelic acid as starting material with acetic anhydride,chlorination of carboxylic acid,condensation with amino-pyridines and deprotection.The reactivity of various amino-pyridines and the deprotection conditions of intermediates 4a-4f were researched.At last,the inhibition rates of 5a-5f against Botrytis cinerea were tested by detecting the mycelium growth rate.Results] The products were obtained in total yields of 76-84%,the structures were confirmed by 1H NMR and IR spectra.The inhibition rates of 5a-5f against Botrytis cinerea were 17-63%.Conclusions] All the amino-pyridines can condense with p-chloro-mandelic acid chloride effectively.The deprotection of 4a-4e can be realized in the condition of sodium hydroxide/ethylalcohol,4f needs more temperate condition of sodium bicarbonate/ethylalcohol due to its sensitivity to alkali.The method provides an effective path to synthesize the N-pyridyl-p-chloro-mandelamides for the advantages of mild conditions and high yields.Bioassay showed that compounds 5a-5f have certain antibacterial effect.