Isolation and structural elucidation of cyclopentynafil and N-octylnortadalafil found in a dietary supplement.
A new sildenafil analogue, cyclopentynafil (1) and a new tadalafil analogue, N-octylnortadalafil (2) were isolated from a dietary supplement illegally marketed for erectile dysfunction. The structures of the sildenafil and tadalafil analogues were elucidated by using HPLC-photodiode array (PDA), LC-MS, high-resolution MS, NMR and circular dichroism (CD). These compounds were determined to be 5-[2-ethoxy-5-(4-cyclopentylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one and (6R,12aR)-2-octyl-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, respectively. Recently, a large number of phosphodiesterase-5 (PDE-5) inhibitors, including their analogues, have been isolated from dietary supplements, while cyclopentynafil and N-octylnortadalafil are the first compounds reported to be new sildenafil and tadalafil analogues, respectively. Quantitative HPLC analysis showed that the contents of 1 and 2 in the product were about 130 mg/tablet (301 microg/mg) and about 27 mg/tablet (64.1 microg/mg), respectively.
Hasegawa
Takashi
T
Chiba Prefectural Institute of Public Health, Chuo-ku, Japan.
Takahashi
Kazunaga
K
Saijo
Masaaki
M
Ishii
Toshiyasu
T
Nagata
Tomoko
T
Kurihara
Masaaki
M
Haishima
Yuji
Y
Goda
Yukihiro
Y
Kawahara
Nobuo
N
D002243:Carbolines / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D019587:Dietary Supplements / Q000032:analysis*; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D013450:Sulfones / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D000068581:Tadalafil
D002243:Carbolines; D013287:Illicit Drugs; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D000068581:Tadalafil; C539047:N-octylnortadalafil; C539046:cyclopentynafil