Synthesis, Inhaltsverzeichnis Synthesis 2025; 57(05): 973-977DOI: 10.1055/s-0043-1775433 psp A Scalable, Chromatography-Free Synthesis of the Potent and Highly Selective ERβ Agonist EGX358 Subhabrata Chaudhury a Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA , Dulanjali Thennakoon b Estrigenix Therapeutics, Inc., 1225 Discovery Parkway, Suite 255C, Wauwatosa, WI 53226, USA , Edward A. Wetzel a Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA , William A. Donaldson ∗ a Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA b Estrigenix Therapeutics, Inc., 1225 Discovery Parkway, Suite 255C, Wauwatosa, WI 53226, USA › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract 4-[trans-4-(Hydroxymethyl)cyclohexyl]phenol (EGX358) is a potent and highly selective estrogen receptor beta (ERβ) agonist which has demonstrated efficacy for moderation of a chemically induced hot flash and for memory consolidation in an ovariectomized mouse model for menopause. An improved synthetic route to EGX358 is reported which proceeds in four steps and which is chromatography-free. Key words Key wordschromatography-free synthesis - Diels–Alder reaction - ionic reduction - estrogen receptor beta agonist - EGX358 Volltext Referenzen References 1 Present address: S. Chaudhury, Biological and Chemical Sciences, College of Arts & Sciences, New York Institute of Technology, New York, NY 10023, USA. 2 Vargas KG, Milic J, Zaciragic A, Wen K, Jaspers L, Nano J, Dhana K, Bramer WM, Kraja B, van Beeck E, Ikram MA, Muka T, Franco OH. Maturitas 2016; 93: 41 3 Walf AA, Frye CA. Pharmacol., Biochem. Behav. 2007; 86: 407 4 Walf AA, Koonce CJ, Frye CA. Behav. Neurosci. 2008; 122: 974 5 Zhao L, Woody SK, Chhibber A. Ageing Res. Rev. 2015; 24: 178 6 Jordan VC. Br. J. Pharmacol. 1993; 110: 507 7 Hanson AM, Perera KL. I. S, Kim J, Pandey RK, Sweeney N, Lu X, Imhoff A, Mackinnon AC, Wargolet AJ, Van Hart RM, Frick KM, Donaldson WA, Sem DS. J. Med. Chem. 2018; 61: 4720 8 Fleischer AW, Schalk JC, Wetzel EA, Hanson AM, Sem DS, Donaldson WA, Frick KM. Horm. Behav. 2021; 130: 104948 9 Schwabe MR, Fleischer AW, Kuehn RK, Chaudhury S, York JM, Sem DS, Donaldson WA, LaDu MJ, Frick KM. Front. Aging Neurosci. 2024; 16: 1477045 10 Barker G, Webster S, Johnson DG, Curley R, Andrews M, Young PC, Macgregor SA, Lee A.-L. J. Org. Chem. 2015; 80: 9807 11 CCDC 2385594 (9) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures 12 Yanagisawa A, Nishimura K, Ando K, Nezu T, Maki A, Kato S, Tamaki W, Imai E, Mohri S.-i. OPR&D 2010; 14: 1182 13a Thompson HW. J. Org. Chem. 1971; 36: 2577 13b Thompson HW, Naipawer RE. J. Org. Chem. 1972; 37: 1307 13c Thompson HW, Rashid SY. J. Org. Chem. 2002; 67: 2813 13d Kraft P, Weymuth C, Nussbaumer C. Eur. J. Org. Chem. 2006; 1403 14 Lee H.-J, Arumugam N, Almansour A, Kumar RS, Maruoka K. Tetrahedron 2018; 74: 5263 15a Crabtree RH, Davis MW. J. Org. Chem. 1986; 51: 2655 15b Shultz AG, McCloskey PJ. J. Org. Chem. 1985; 50: 5907 Zusatzmaterial Zusatzmaterial Supporting Information
