14 research outputs found
Tandem construction of carbon-carbon and carbon-oxygen bonds in the Baylis-Hillman chemistry: synthesis of functionalized dl-bis-allyl ethers
Tandem coupling between acrylonitrile and aryl aldehydes under the catalytic influence of DABCO involving the construction of two carbon-carbon bonds and one carbon-oxygen bond leading to the synthesis of dl-functionalized bis-allyl ethers has been described
Reactivity of Acyclic (pentadienyl)iron(1+) Cations with Phosphonate Stabilized Nucleophiles: Application to the Synthesis of Oxygenated Metabolites of Carvone
The addition of phosphonate stabilized carbon nucleophiles to acyclic (pentadienyl)iron(1+) cations proceeds predominantly at an internal carbon to afford (pentenediyl)iron complexes. Those complexes bearing an electron withdrawing group at the Ļ-bound carbon (i.e., 13/14) are stable and isolable, while complexes which do not contain an electron withdrawing group at the Ļ-bound carbon undergo CO insertion, reductive elimination and conjugation of the double bond to afford cyclohexenone products (21/22). Deprotonation of the phosphonate 13/14 or 21 and reaction with paraformaldehyde affords the olefinated products. This methodology was utilized to prepare oxygenated carvone metabolites (Ā±)-25 and (Ā±)-26
Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system
A diastereoselective route to the 5,7,5-tricyclic core of the guianolides is presented. This route relies on Cope rearrangement of a divinylcyclopropane prepared by alkenyl Grignard addition to a (pentadienyl)iron(+1) cation, followed by oxidative decomplexation. An additional key reaction involves oxidative rearrangement of a 3,4-epoxy-1,7-diol to generate a Ī³-lactone. The relative stereochemistry of this product was established by X-ray crystallography
Probing the Human Estrogen Receptor-Ī± Binding Requirements for Phenolic Mono- and Di-Hydroxyl Compounds: A Combined Synthesis, Binding and Docking Study
Various estrogen analogs were synthesized and tested for binding to human ERĪ± using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERĪ±. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERĪ² over ERĪ±, and was also 25-fold specific for agonist ERĪ² versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERĪ², versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERĪ± with high affinity, via hydroxyl hydrogen bonding interactions with the ERĪ± Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule
Spectral Data for Probing the human estrogen receptor-alpha binding requirements for phenolic mono- and do-hydroxyl compounds: A combined synthesis, binding and docking study
Spectral data used in the course of researching Probing the human estrogen receptor-alpha binding requirements for phenolic mono- and do-hydroxyl compounds: A combined synthesis, binding and docking study .
Various estrogen analogs were synthesized and tested for binding to human ERĪ± using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERĪ±. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERĪ² over ERĪ±, and was also 25-fold specific for agonist ERĪ² versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERĪ², versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERĪ± with high affinity, via hydroxyl hydrogen bonding interactions with the ERĪ± Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule
Probing the Human Estrogen Receptor-Alpha Binding Requirements for Phenolic Mono- and di-Hydroxyl compounds: A Combined Synthesis, Binding and Docking Study
Various estrogen analogs were synthesized and tested for binding to human ERĪ± using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERĪ±. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERĪ² over ERĪ±, and was also 25-fold specific for agonist ERĪ² versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERĪ², versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERĪ± with high affinity, via hydroxyl hydrogen bonding interactions with the ERĪ± Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule
Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles
The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3 + 2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e
A novel and effective chiral phosphoramide catalyst for the borane-mediated asymmetric reduction of prochiral α-halo ketones
The novel chiral phosphoramide, 1,4-bis[(5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octan-2-yl]piperazine, was synthesised and successfully employed as a catalyst in the borane-mediated asymmetric reductions of prochiral α-halo ketones, providing the corresponding α-halo alcohols in 90-95% enantiomeric purities
(2S,5S)-1,3-Diaza-2-phospha-2-oxo-2-chloro-3-phenylbicyclo[3.3.0]octane: a novel chiral source for borane-mediated catalytic chiral reductions
(2S,5S)-1,3-Diaza-2-phospha-2-oxo-2-chloro-3-phenylbicyclo[3.3.0]octane has been successfully employed as a chiral catalytic source for the borane mediated asymmetric reductions of prochiral α-halo ketones to provide the desired (S)-secondary alcohols in 81-91% enantiomeric purities, thus for the first time demonstrating the potential of the N-P(=O)Cl structural framework to generate a recoverable, reusable and air stable catalyst for the asymmetric reduction processes
The first intramolecular friedel-crafts reaction of Baylis-Hillman adducts: synthesis of functionalized indene and indane derivatives
The first intramolecular Friedel-Crafts reaction of the Baylis-Hillman adducts using P<SUB>2</SUB>O<SUB>5</SUB> leading to the formation of functionalized indene derivatives and subsequent hydrogenation providing indane derivatives have been described