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

在本项目中，我研究了光学活性荧光喹恶啉的合成及其在高灵敏度外消旋羧酸光学纯度测定试剂中的应用。新合成了C-6位含氨基酸残基的手性2，3-二吗啉喹恶啉。2.用Mukaiyama方法进行了D，L-萘普生，-布洛芬，-2-苯丙酸与含L氨基酸残基的手性喹恶啉的衍生化反应，得到了发出强烈荧光的非对映异构体。3.当激发波长为370 nm左右时，非对映异构体的荧光峰值出现在440 nm左右。4.与MeCN.5相比，MeCN水溶液中的荧光强度显著降低。以菲为标准，用相对量子产额法测得荧光的量子产额为0.052。6.D，L-萘普生、-布洛芬、-2-苯丙酸与带有L-脯氨酸残基的手性喹恶啉的非对映异构体均可在16分钟内在装有荧光检测器的反相高效液相色谱(Finepak SilL C_&lt；18&gt；S)上得到清晰分离。7.在L/N=5的条件下，对映异构体的检出限为5pmoL/10μS。结论：含氨基酸残基的光学活性荧光喹恶啉类化合物可用于新型高灵敏度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.