59875-94-4Relevant articles and documents
Oxidative umpolung ?±-alkylation of ketones
Shneider, O. Svetlana,Pisarevsky, Evgeni,Fristrup, Peter,Szpilman, Alex M.
supporting information, p. 282 - 285 (2015/03/05)
We disclose a hypervalent iodine mediated ?±-alkylative umpolung reaction of carbonyl compounds with dialkylzinc as the alkyl source. The reaction is applicable to all common classes of ketones including 1,3-dicarbonyl compounds and regular ketones via their lithium enolates. The ?±-alkylated carbonyl products are formed in up to 93% yield. An ionic mechanism is inferred based on meticulous analysis, NMR studies, trapping and crossover experiments, and computational studies.
Base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes
Sanchez-Carmona, Miguel A.,Contreras-Cruz, David A.,Miranda, Luis D.
, p. 6506 - 6508 (2011/11/05)
We describe a convergent, base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes in a three-component process. The synthetic potential of this protocol was underscored by the
Pyrazole ligands: Structure - Affinity/activity relationships and estrogen receptor-α-selective agonists
Stauffer,Coletta,Tedesco,Nishiguchi,Carlson,Sun,Katzenellenbogen,Katzenellenbogen
, p. 4934 - 4947 (2007/10/03)
We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERα than on the ERβ subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERα-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERα. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERα with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ERα. It also activates gene transcription only through ERα. Thus, this compound represents the first ERα-specific agonist. We investigated the molecular basis for the exceptional ERα binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ERα with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERα has a smaller residue than ERβ. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERα.
