Tafesse Laykea, Kyle Donald J
Discovery Research, Purdue PharmaLP, Cranbury, NJ 08512, USA.
Comb Chem High Throughput Screen. 2004 Mar;7(2):151-9. doi: 10.2174/138620704773120838.
Capsazepine (CPZ, 1) is a well-known vanilloid receptor (VR1) antagonist that has been cited widely used in the literature. However the current synthetic methods used for the total synthesis of CPZ are lengthy, involve multiple purification steps, and produce low yields. Here we describe a new and highly efficient synthesis of benzazepine 3, a synthetic precursor of CPZ, in only two steps and 59% overall yield from a commercially available tetralone 2 via a Schmidt reaction as a key step. Moreover, we apply parallel synthesis techniques to prepare CPZ and CPZ analogs. Our approach enables the possibility of preparing larger, and more diverse libraries of CPZ analogs.
辣椒平（CPZ，1）是一种著名的香草酸受体（VR1）拮抗剂，在文献中被广泛引用。然而，目前用于CPZ全合成的方法冗长，涉及多个纯化步骤，且产率较低。在此，我们描述了一种新型高效合成苯并氮杂䓬3的方法，苯并氮杂䓬3是CPZ的合成前体，以市售的四氢萘酮2为原料，通过关键步骤施密特反应，仅两步即可完成合成，总产率为59%。此外，我们应用平行合成技术制备CPZ及其类似物。我们的方法使得制备更大、更多样化的CPZ类似物库成为可能。
