Synthesis and Structure Revision of Dimeric Tadalafil Analogue Adulterants in Dietary Supplements

Suresh Mandava; Bogonda Ganganna; Jungjoong Hwang; Younchang Jang; Jiho Hwang; Mallesham Samala; Ki-Bbeum Kim; Haeil Park; Ji Hyun Lee; Sun Young Baek; Jongkook Lee

doi:10.1248/cpb.c17-00034

Regular Articles

Synthesis and Structure Revision of Dimeric Tadalafil Analogue Adulterants in Dietary Supplements

Suresh Mandava, Bogonda Ganganna, Jungjoong Hwang, Younchang Jang, Jiho Hwang, Mallesham Samala, Ki-Bbeum Kim, Haeil Park, Ji Hyun Lee, Sun Young Baek, Jongkook Lee

Author information

Suresh Mandava
College of Pharmacy, Kangwon National University
Bogonda Ganganna
College of Pharmacy, Kangwon National University
Jungjoong Hwang
College of Pharmacy, Kangwon National University
Younchang Jang
College of Pharmacy, Kangwon National University
Jiho Hwang
College of Pharmacy, Kangwon National University
Mallesham Samala
College of Pharmacy, Kangwon National University
Ki-Bbeum Kim
College of Pharmacy, Kangwon National University
Haeil Park
College of Pharmacy, Kangwon National University
Ji Hyun Lee
Advanced Analysis Team, Toxicological Evalauation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety
Sun Young Baek
Advanced Analysis Team, Toxicological Evalauation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety
Jongkook Lee Corresponding author
College of Pharmacy, Kangwon National University

Keywords: phosphodiesterase 5 inhibitor, bisprehomotadalafil, bisprecyclopentyltadalafil, bisprenortadalafil, dietary supplement

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Supplementary material

2017 Volume 65 Issue 5 Pages 498-503

DOI https://doi.org/10.1248/cpb.c17-00034

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Abstract

A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.

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