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Synthesis and evaluation of opioid receptor-binding affinity of elaeocarpenine and its analogs
Haruaki Kurasaki1, Iwao Okamoto, Nobuyoshi Morita
1Exploratory Research Laboratories, Kyorin Pharmaceutical Co., Ltd 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
Abstract:
Both enantiomers of elaeocarpenine (1) and its analogs, 21, 22, 25, and 27, were synthesized from bicyclic aldehydes 8-10 via a flexible route previously established for total synthesis of grandisines, and their binding affinities for mu-, kappa- and delta-opioid receptor subtypes were evaluated. We found that (9R)-1 exhibited higher affinity than (9S)-1 for all the subtypes, but the enantiomers showed little subtype selectivity. Analogs 21 having a pyrrolizidine skeleton and 27 having a stemona-type skeleton in place of the indolizidine unit of (9S)-1 showed mu-selective and mu-, kappa-selective binding, respectively.
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