971-82-4Relevant articles and documents
Steroidal affinity labels of the estrogen receptor. 1. 17α- (Bromoacetoxy)alkyl/alkynylestradiols
El Garrouj,Aumelas,Borgna
, p. 2973 - 2983 (1993)
To develop steroidal affinity labels for the estrogen receptor, we prepared five electrophilic estradiol derivatives bearing the 17α-propyl, 17α-(1'-butynyl), or 17α-(1'-octynyl) chain, with either a terminal epoxy function (for the 17α-propyl substituent) or a terminal bromoacetoxy function (for all three 17α-substituent types). These compounds displayed low affinity for the lamb uterine estrogen receptor; with apparent relative affinity constants ranging from 0.02% to 0.24% that of estradiol. They were also rapidly transformed in cytosol, probably to the corresponding vicinal diols (epoxy compounds) or primary alcohols (bromoacetoxy compounds). Nevertheless, bromoacetates induced irreversible inactivation of the hormone- binding site but only with ligand-free binding sites. The effect of bromoacetates was prevented by treatment of the cytosol with the thiol- specific reagent methyl methanethiosulfonate. Inactivation of the receptor at 0 °C was rapid (150 nM (at pH 9) or pH > 7.5 (at 5 μM). Regardless of the conditions used, the order of efficiency for bromoacetates was always: 17α-propyl derivative 17α-butynyl derivative 17α-octynyl derivative, with maximal inactivation of ~30% and ~70% of the hormone-binding sites obtained for the less active and more active compounds, respectively. Characteristics of the receptor inactivation suggest that (i) prepared bromoacetates are highly reactive affinity labels for the estrogen receptor, (ii) they react with similar (or even a single) nucleophilic amino acid residues located within or near the hormone-binding site of the receptor; these residues are probably the -SH of cysteines, and (iii) position 17α of steroidal ligands is suitable for introducing electrophilic substituents to develop efficient affinity labels for the receptor.
Ti-catalyzed Barbier-type allylations and related reactions
Estevez, Rosa E.,Justicia, Jose,Bazdi, Btissam,Fuentes, Noelia,Paradas, Miguel,Choquesillo-Lazarte, Duane,Garcia-Ruiz, Juan M.,Robles, Rafael,Gansaeuer, Andreas,Cuerva, Juan M.,Oltra, J. Enrique
experimental part, p. 2774 - 2791 (2009/12/03)
Titanocene(III) complexes, easily generated in situ from commercial Ti IV precursors, catalyze Barbiertype allylations, intramolecular crotylations (cyclizations), and prenylations of a wide range of aldehydes and ketones. The reaction displays surprising and unprecedented mechanistic subtleties. In cyclizations a fast and irreversible addition of an allyl radical to a TiIII-coordinated carbonyl group seems to occur. Intermolecular additions to conjugated aldehydes proceed through a coupling of a Ti IV-bound ketyl radical with an allyl radical. Reactions of ketones with allylic halides take place by the classical addition of an allylic organometallic reagent. The radical coupling processes enable transformations such as the highly regioselective α-prenylation that are otherwise difficult to achieve. The mild reaction conditions and the possibility to employ titanocene complexes in only catalytic quantities are highly attractive features of our protocol. These unusual properties have been taken advantage of for the straightforward synthesis of the natural products rosiridol, shikalkin, and 12-hydroxysqualene.
