An efficient parallel synthesis of capsazepine and capsazepine analogs.
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.
Tafesse
Laykea
L
Discovery Research, Purdue PharmaLP, Cranbury, NJ 08512, USA. laykea.tafesse@pharma.com
Kyle
Donald J
DJ
D001552:Benzazepines / Q000138:chemical synthesis; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D001552:Benzazepines; C071423:capsazepine; D002211:Capsaicin