Synthesis of Novel 13α-estrone Derivatives by Sonogashira Coupling As Potential 17β-HSD1 Inhibitors

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2017 Jul 12

PMID 28694873

Citations 8

Authors

Ildiko Bacsa

Rebeka Jojart

Janos Wolfling

Gyula Schneider

Bianka Edina Herman

Mihaly Szecsi

Erzsebet Mernyak

Affiliations

Soon will be listed here.

Abstract

Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with -substituted phenylacetylenes using Pd(PPh) as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh)Cl. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC values.

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