Subscribe to RSS
Download PDF
DOI: 10.1055/a-2698-0726
Total Synthesis of (±) Pimeforazine A and B
We are grateful to the Science and Engineering Research Board (SERB), India, for financial support (CRG/2022/004763) and the Indian Institute of Technology Hyderabad for providing facilities.
Abstract
Racemic pimeforazine A (1) and B (2), neuroprotective compounds isolated from the weevil Pimelocerus perforatus, have attracted interest due to their potent biological activity. We report the first total synthesis of (±)-pimeforazine A and B, along with 16 structurally related analogues, starting from hydroxytyrosol. The key steps include the in-situ generation of a reactive electrophilic quinone intermediate from hydroxytyrosol, followed by a nucleophilic Michael addition with selected ortho-aminophenols. This one-pot transformation proceeds under mild aqueous conditions, utilizing molecular oxygen as the sole oxidant.
Keywords
Hydroxytyrosol - Biomimetic oxidation - Michael addition - Neuroprotective natural products - Quinone intermediates - Molecular oxygen oxidationPublication History
Received: 07 August 2025
Accepted after revision: 08 September 2025
Accepted Manuscript online:
08 September 2025
Article published online:
22 September 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1 Canter RG, Penney J, Tsai L-H. Nature 2016; 539: 187
- 2 Duyckaerts C, Delatour B, Potier M-C. Acta Neuropathol 2009; 118: 5
- 3 Butterfield DA, Halliwell B. Nat Rev Neurosci 2019; 20: 148
- 4 Vu Nguyen K. Neuroscientist 2018; 5: 74
- 5 Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Arch Neurol 2003; 60: 1119
- 6 Wancata J, Musalek M, Alexandrowicz R, Krautgartner M. Eur Psychiatry 2003; 18: 306
- 7 Kamil K, Kumar J, Yazid MD, Hj Idrus R. J Sex Med 2018; 47: 2811
- 8 Romero-Márquez JM, Navarro-Hortal MD, Forbes-Hernández TY. et al. Antioxidants 2023; 12: 1538
- 9 Fujikawa A, Ishihara Y, Ohta E. et al. J Nat Prod 2022; 85: 2740
- 10 Wani TA, Masoodi FA, Gani A. et al. Trends Food Sci Technol 2018; 77: 77
- 11 Ramírez-Tortosa MC, Ramirez-Perez C, Gaforio JJ, Quiles JL, Moreno JA, Ramirez-Tortosa CL. Med Diet 2020; 165
- 12 Bernini R, Mincione E, Barontini M, Crisante F. J Agric Food Chem 2008; 56: 8897
- 13 Zhang Z-L, Chen J, Xu Q, Rao C, Qiao C. Synth Commun 2012; 42: 794
- 14 Ziosi P, Paolucci C, Santarelli F. et al. ChemSusChem 2018; 11: 2202
- 15 Zhao J, Liu G, Sun J, Wang Q, Li Z-J, Yang X. Anal Chem 2020; 92: 2316
- 16 Acuña AU, Álvarez-Pérez M, Liras M, Coto PB, Amat-Guerri F. Phys Chem Chem Phys 2013; 15: 16704
- 17 Acuña AU, Amat-Guerri F, Morcillo P, Liras M, Rodríguez B. Org Lett 2009; 11: 3020
- 18 Cavalieri EL, Li K-M, Balu N. et al. Carcinogenesis 2002; 23: 1071
- 19 Ito S, Sugumaran M, Wakamatsu K. Int J Mol Sci 2020; 21: 6080
- 20 Hayat F, Kang L, Lee C-Y, Shin D. Tetrahedron 2015; 71: 2945
- 21 Kiruthika SE, Perumal PT. Org Lett 2014; 16: 484
- 22 Yang Z, Tan F, Wong H. WO 2012/006783 A1 (PCT/CN2010/075180) 2012
- 23 Kornberg BE, Lewthwaite RA, Manning DD, Nikam SS, Scott IL. WO 2023/115149 A1 2023
- 24 Markus A, Schepmann D, Wünsch B. Arch Pharm 2022; 355: 2200020