HOBt,HOOBt,HOSu与惰性氯代烷溶剂之间的反应及其对多肽合成影响的研究

Studies on the Reaction of HOBt, HOOBt and HOSu with Chloroalkane Solvents and Their Affects on the Peptide Synthesis

HOBt,HOSu,HOOBt是多肽合成中常用的试剂,它们常被用作羧基活化试剂和消旋抑制剂首次发现HOBt,HOSu,HOOBt在碱的存在下可与氯代烷烃溶剂发生反应,并系统地研究了不同的反应条件对产率的影响和对多肽合成的影响.发现反应的产率与碱的用量,反应温度,反应物等因素有关,碱性越强,反应速度越快产率越高,HOBt较易反应,HOSu较为稳定,二氯甲烷易生成双取代产物,1,2-二氯乙烷易生成单取代产物,所有产物均经硅胶柱层析分离纯化,共合成8个新化合物并通过光谱鉴定.虽然在模型二肽BocAlaPheOCH3合成反应中检测到少量副产物的产生,但二肽的产率＞82%c.

HOBt, HOSu and HOOBt are the widely used reagents in the peptide synthesis, they are used as the activitor of carboxyl group and the inhibitor of racemization. HOBt, HOSu and HOOBt were found for the first time that they could react with chloroalkane solvents in the presence of different bases. The yields were related to the reaction condition such as the quantity and variety of bases, reaction temperature and the structure of the reactants. The more of the bases used, the higher of the yield and reaction speed. HOBt is more active than HOSu, CH2Cl2 is easy to form disubstituted products, ClCH2CH2Cl is easy to form monosubstituted products. All of the products were purified by chromatography on silica - gel, eight new compounds were identified by MS and H-1 NMR. In the model synthesis of dipeptide BocAlaPheOCH(3), the by - product was detected and the yield of the dipeptide was over 82%.