Organometallic Complexes Containing 17-Ethynyl-17β-hydroxyandrost-4-en-3-one and Related Ethynyl Steroids

Abstract

Gold complexes of 17-ethynyl-17β-hydroxyandrost-4-en-3-one, 17-ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol, and 17α-ethynylestra-1,3,5(10)-triene-3,17β-diol have been prepared and characterized. The title compounds were prepared by treatment of the parent ethynyl steroid with sodium bis(trimethylsilyl)amide followed by the addition of R3PAuCl. Using a variety of phosphorus donors, a total of 36 gold steroid compounds were readily prepared using this approach. Compounds containing basic low cone angle phosphines such as PMe3 and PEt3 exhibited broad signals in the 13C{1H} NMR spectrum for the alkyne moiety, while compounds containing triarylphosphines or moderately bulky trialkylphosphines exhibited sharp signals. Correlations between common measures of phosphine donor ability with 2 J CP and 3 J CP as well as changes in the 31P chemical shift were made. While the use of low cone angle phosphines was successful, analogous reactions with trimesitylphosphine or tris(2,4,6-trimethoxyphenyl)phosphine resulted in intractable mixtures containing significant amounts of free phosphine. The incorporation of electron-withdrawing groups into the organic fragment of the phosphine donors was tolerated except for P(C6F5)3, where displacement of the phosphine was observed. The molecular structures of five representative examples are presented and discussed. These determinations represent the first structurally characterized examples where the transition metal is σ-bound to the ethynyl fragment of the steroid.

P–H activation using alkynylgold substrates: steric and electronic effects

“…Reductive elimination would afford the observed products. Our own attempts to effect an oxidative addition reaction between aryl halides and gold substituted ethynylsteroids 78 were unsuccessful and only starting materials were recovered. These observations were supported by a recent report which outlined problematic oxidative addition reactions of aryl halides to gold(I) centers.…”

Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones

“…Recently we have witnessed a revival of gold complexes in medicinal chemistry and new results have demonstrated that gold complexes are promising anticancer [15,16,17,18] and antimicrobial [19,20] drug candidates. The majority of biologically tested gold complexes focus on gold ions in the +1 oxidation state and generally bound to thiolates [21,22], to various N -heterocyclic carbenes (NHC) [23,24,25,26,27], to diphos-type [28] and alkyne [29,30,31,32,33,34,35] ligands. There is also an increased interest in the development of anticancer gold(III)-NHC complexes [36,37,38].…”

“…These alterations ultimately lead to the pro-apoptic proteins signalling induction [27,40,42]. In comparison to the other classes of biologically investigated gold(I) complexes [15,18,19,20,23,24,25,26,27,40,41] gold(I)-alkynyl complexes have been studied to the very limited extent [29,30,31,32,33,34,35]. Moreover, to the best of our knowledge to date there has not been any reported data on the antibacterial activity of gold(I)-alkynyl complexes although some in vitro antimalarial activity in two strains of Plasmodium falciparum has been published [32].…”

Heterobimetallic propargyl gold complexes with π-bound copper or silver with enhanced anticancer activity

“…3,4 Of the gold(I) complexes reported to have anti-cancer activity, alkynyl-gold(I)-phosphine complexes are among the most potent. [5][6][7][8][9][10][11][12][13][14] The incorporation of a second different metal centre into a complex can alter the physiochemical properties significantly. This can be advantageous in the development of chemothera- For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d0dt02113j peutic agents as a means of enhancing cytotoxicity.…”