Synthesis of DL-standishinal and its related compounds for the studies on structure-activity relationship of inhibitory activity against aromatase.
DL-Standishinal (1), an aromatase inhibitor isolated from Thuja standishii, was synthesized in 15 steps from p-formylanisole via aldol reaction of 12-hydroxy-6,7-secoabieta-8,11,13-trien-6,7-dial (2). In the present study, we found that the aldol condensation of 2 proceeded in excellent yield with the protonic catalyst such as d-camphorsulfonic acid in CH(2)Cl(2). Moreover, structure-activity relationship of 1 and its related compounds was studied and it was revealed that the isomers having cis-configuration on the A/B-ring generally exhibited more potent inhibitory activities against aromatase than those with trans-configuration.
Katoh
Takahiro
T
Department of Pharmaceutical Manufacturing Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, 1 Shichono-cho, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Akagi
Taichi
T
Noguchi
Chie
C
Kajimoto
Tetsuya
T
Node
Manabu
M
Tanaka
Reiko
R
Nishizawa née Iwamoto
Manabu
M
Ohtsu
Hironori
H
Suzuki
Noriyuki
N
Saito
Koichi
K
D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D029783:Thuja / Q000737:chemistry
D047072:Aromatase Inhibitors; D004224:Diterpenes; D007202:Indicators and Reagents; C467918:standishinal