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 σ-bound carbon (i.e., 13/14) are stable and isolable, while complexes which do not contain an electron withdrawing group at the σ-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 (±)-25 and (±)-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 γ-lactone. The relative stereochemistry of this product was established by X-ray crystallography

Probing the Human Estrogen Receptor-α 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 ERα 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 ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, 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 ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα 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 ERα 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 ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, 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 ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα 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 ERα 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 ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, 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 ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα 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