Gong Young-Dae, Seo Jin-Soo, Chon Yong Sog, Hwang Jong Yeon, Park Ji Yeon, Yoo Sung-Eun
Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusung, Taejon 305-600, Korea.
J Comb Chem. 2003 Sep-Oct;5(5):577-89. doi: 10.1021/cc030014b.
We report the solid-phase library construction of 2000 analogues of 6-amino-2,2-dimethyl-3,4,6-trisubstituted-2H-1-benzopyran. The polymer-bound hydroxyalkoxychromanes 5, produced by nucleophilic reactions with various alcohols on epoxides generated in situ, served as key intermediates for subsequent diversification. Further reactions on these hydroxyalkoxychromanes 5 with various electrophiles, such as alkyl halides and acid halides, produced the desired 6-amino-2,2-dimethyl-3,4,6-trisubstituted-2H-1-benzopyran analogues 9, 10, and 11. The progress of reactions could be monitored as solid-bound intermediates by ATR-FTIR or HR-MAS-NMR spectroscopy. The final compounds, obtained in good yields and high purity upon cleavage from the resins, were characterized by LC/MS, HRMS, (1)H NMR, and (13)C NMR spectroscopy.
我们报道了6-氨基-2,2-二甲基-3,4,6-三取代-2H-1-苯并吡喃2000种类似物的固相库构建。通过与各种醇对原位生成的环氧化物进行亲核反应制备的聚合物负载的羟基烷氧基色满5，作为后续多样化的关键中间体。这些羟基烷氧基色满5与各种亲电试剂（如卤代烷和酰卤）的进一步反应，生成了所需的6-氨基-2,2-二甲基-3,4,6-三取代-2H-1-苯并吡喃类似物9、10和11。反应进程可以通过衰减全反射傅里叶变换红外光谱（ATR-FTIR）或高分辨魔角旋转核磁共振光谱（HR-MAS-NMR）对固载中间体进行监测。从树脂上裂解后以良好产率和高纯度得到的最终化合物，通过液相色谱/质谱（LC/MS）、高分辨质谱（HRMS）、氢核磁共振（1H NMR）和碳核磁共振（13C NMR）光谱进行表征。
