Studies on Development of High-sensitive Optical Purity Determination Reagents Using Optically Active Fluorescent Quinoxalines

本课题研究了光活性荧光喹诺啉类化合物的合成及其在外消旋羧酸高灵敏度光学纯度测定试剂中的应用。新合成了具有C-6位氨基酸残基的手性2,3-二morpholinoquinoxalines。2. 用Mukaiyama法将D、l -萘普生、-布洛芬和-2-苯基丙酸与含l -氨基酸残基的手性喹诺啉衍生物衍生，得到了具有强荧光的非对映体。3. 当激发波长为370 nm左右时，非对映体的荧光最大值出现在440 nm左右。4. 与men .5相比，men水溶液中的荧光强度明显降低。采用以蒽为标准的相对量子产率法测定荧光量子产率为0.052。6. D、l -萘普生、-布洛芬和-2-苯基丙酸与手性喹诺啉（含l -脯氨酸残基）的非对映体在16 min内用荧光检测器（Finepak SIL C_<18>S）反相高效液相色谱（HPLC）分离得到。7. 在信噪比为5的条件下，该非对映体的检出限为5 pmol/10 μl。综上所述，带有氨基酸残基的光学活性荧光喹诺啉类化合物可用于新型高灵敏度的手性羧酸光学纯度测定试剂。

In this project, I investigated synthesis of optically active fluorescent quinoxalines and their application to high-sensitive optical purity determination reagents for racemic carboxylic acids.1. Chiral 2,3-dimorpholinoquinoxalines bearing amino acid residues at C-6 position were newly synthesized. 2. The derivatization of D,L-naproxen, -ibuprofen, and -2-phenylpropionic acid with chiral quinoxalines bearing L-amino acid residues was carried out by using the Mukaiyama method to give the diastereomers, which emitted intense fluorescence. 3. Fluorescence maxima of the diastereomers appeared around 440 nm when the excitation wavelength of about 370 nm was applied. 4. The fluorescence intensity in aqueous MeCN solution was remarkably decreased compared with that in MeCN.5. The quantum yield of fluorescence was measured to be 0.052 by using the relative quantum yield measurement with anthracene as a standard. 6. All the diastereomers derived from D,L-naproxen, -ibuprofen, and -2-phenylpropionic acid with chiral quinoxaline bearing the L-prolin residue were clearly separated within 16 min on reversed-phase (Finepak SIL C_<18>S) HPLC equipped with a fluorescence detector. 7. The detection limit of the diastereomer was estimated to be 5 pmol/10 μl injection volume on the S/N ratio of 5.In conclusion, optically active fluorescent quinoxalines bearing the amino acid residue were demonstrated to be applicable to new high-sensitive optical purity determination reagents for chiral carboxylic acids.