A twist on facial selectivity of hydride reductions of cyclic ketones: twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions.
ABSTRACT: The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin-Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride).
Project description:The origins of ?-facial selectivities in the borohydride reduction of endocyclic iminium ions have been elucidated by density functional theory calculations. In reductions of conjugated ("thermodynamic") iminium ions, the ?-facial preference of the hydride attack was found to be due to torsional steering. Attack at the favored ?-face leads to a lower-energy "half-chair"-like conformation of the tetrahydropyridine product, whereas attack at the other ?-face results in an unfavorable "twist-boat" conformation. In reductions of nonconjugated ("kinetic") iminium ions, torsional distinction is small between the top- and bottom-face attacks, and the ?-facial selectivity of the hydride approach is primarily due to steric hindrance.
Project description:In the title compound, [FeRu(C(17)H(14)P)(2)(C(6)H(8)BN(4))H(CO)]·C(3)H(6)O, the Ru(II) ion is coordinated in a distorted octa-hedral environment involving a hydride ligand, a carbonyl ligand and two bidentate ligands. Of the two bidentate ligands, the bulky 1,1'-bis-(diphenyl-phosphino)ferrocene (dppf) ligand chelates with a larger bite angle of 101.90?(2)°, whereas the bite angle of the [H(2)Bpz(2)](-) ligand (pz = pyrazol-yl) is 85.67?(7)°. The latter ligand creates an RuN(4)B six-membered ring with a boat conformation, which puckers towards the site of the small hydride ligand. The hydride ligand is cis with respect to the carbonyl ligand and trans to one of the P atoms of the dppf ligand. In the crystal structure, there are weak inter-molecular C-H?O hydrogen bonds between complex mol-ecules and acetone solvent mol-ecules.
Project description:We have developed a new enantioselective C-3 allylation of 3-substituted indoles using allyl alcohol and trialkylboranes. Asymmetric syntheses of 3,3-disubstituted indolines and indolenines in enantiomeric excesses up to 90% have been achieved using the bulky borane 9-BBN-C6H13 as the promoter of the reaction. The dependence of the selectivity on the nature of the borane suggests that the boron reagent has a role beyond promoting ionization of the allyl alcohol. A protocol for oxidation of indolenines to oxindoles has also been developed and led to a formal synthesis of (-)-phenserine.
Project description:Alterations of TWIST-1 expression are often seen in solid tumors and contribute to tumorigenesis and cancer progression. However, studies concerning its pathogenic role in leukemia are scarce. Here we show that TWIST-1 is a new candidate gene contributing to leukemogenesis of myeloid leukemia. We used array as one tool to determine gene expression profiles of control and TWIST-1-overexpressing U937 cells. Overall design: U937 cell line was transduced with TWIST-1 or empty vector. GFP+ cells were sorted. Microarray was performed at GMINIX in Shanghai. Total RNA was isolated with TRIzol reagent (Invitrogen, Canada) and purified using RNeasy Mini Kit (Qiagen, German), including a DNase digestion treatment. RNA concentrations were determined by NanoDrop 2000 (Thermo, America). RNA was labeled using the GeneChip® WT Terminal Labeling and Controls Kit combined with the Ambion® WT Expression Kit. Labeled cRNA was hybridized to GeneChip® Human Transcriptome Array 2.0 arrays (Affymetrix, America).
Project description:cis-2-Methyl-6-substituted piperidin-3-ol alkaloids of the Cassia and Prosopis species are readily prepared by a combination of an aza-Achmatowicz oxidative rearrangement and dihydropyridone reduction followed by a stereoselective allylsilane addition to a N-sulfonyliminium ion. The stereochemical outcome of the reduction reaction can be attributed to steric hindrance between the pseudoaxially oriented 2,6-substituents and the equatorially approaching hydride reagent which explains the exclusive formation of the cis-alcohol by axial approach of the hydride. The unsaturation present in the (E)-methyl-pent-3-enoate side chain was removed by catalytic reduction, and the remaining ester group was converted to the corresponding Weinreb's amide. This key intermediate was utilized for the synthesis of azimic acid, deoxocassine, cassine, and spicigerine. The facile preparation of (S)-N-tosylamidofuran 16 and its conversion to the chiral Achmatowicz oxidation product 18 provide a formal chiral synthesis of these alkaloids.
Project description:Members of the Twist-family of bHLH proteins play a pivotal role in a number of essential developmental programs. Twist-family bHLH proteins function by dimerizing with other bHLH members and binding to cis- regulatory elements, called E-boxes. While Twist-family members may simply exhibit a preference in terms of high-affinity binding partners, a complex, multilevel cascade of regulation creates a dynamic role for these bHLH proteins. We summarize in this review information on each Twist-family member concerning expression pattern, function, regulation, downstream targets, and interactions with other bHLH proteins. Additionally, we focus on the phospho-regulatory mechanisms that tightly control posttranslational modification of Twist-family member bHLH proteins.
Project description:We present a Monte Carlo simulation study of the distribution and propagation of twist from one DNA linker to another for a two-nucleosome array subjected to externally applied twist. A mesoscopic model of the array that incorporates nucleosome geometry along with the bending and twisting mechanics of the linkers is employed and external twist is applied in stepwise increments to mimic quasistatic twisting of chromatin fibers. Simulation results reveal that the magnitude and sign of the imposed and induced twist on contiguous linkers depend strongly on their relative orientation. Remarkably, the relative direction of the induced and applied twist can become inverted for a subset of linker orientations-a phenomenon we refer to as "twist inversion". We characterize the twist inversion, as a function of relative linker orientation, in a phase diagram and explain its key features using a simple model based on the geometry of the nucleosome/linker complex. In addition to twist inversion, our simulations reveal "nucleosome flipping", whereby nucleosomes may undergo sudden flipping in response to applied twist, causing a rapid bending of the linker and a significant change in the overall twist and writhe of the array. Our findings shed light on the underlying mechanisms by which torsional stresses impact chromatin organization.
Project description:The title compound, C26H38N5P, was synthesized by reacting 2-chloro-1,3-bis-(2,6-diiso-propyl-phen-yl)-1,3,2-di-aza-phospho-lidine with sodium azide and a catalytic amount of lithium chloride in tetra-hydro-furan. The title compound is the first structurally characterized 2-azido-1,3,2-di-aza-phospho-lidine and exhibits a P atom in a trigonal pyramidal geometry. The azide P-N bond length of 1.8547?(16)?Å is significantly longer than the P-N separations for the chelating di-amine [P-N = 1.6680?(15) and 1.6684?(14)?Å]. The sterically hindered 2,6-diiso-propyl-phenyl groups twist away from the central heterocycle, with dihedral angles between the central heteocyclic ring and benzene rings of 76.17?(10) and 79.74?(9)°. In the crystal, a weak C-H?N link to the terminal N atom of the azide group leads to  chains.
Project description:A simple, efficient and highly diastereoselective one-pot three-component synthesis of functionalized 2,6-disubstituted-4-tosyloxytetrahydropyrans was performed. The synthesis features an optimized Prins cyclization in which an aromatic homoallylic alcohol, an aromatic/aliphatic aldehyde, and p-toluenesulfonic acid (catalyst and reagent) are reacted in the presence of molecular sieves (MS) 4 Å at reflux in dichloromethane to afford excellent yields (72-96%) within short reaction times (20-90 min). The MS 4 Å-promoted synthesis proved to be versatile enough to provide an array of symmetrical and unsymmetrical tetrahydropyran derivatives in economical manner. Furthermore, cleavage of the 4-tosyl group under mild conditions afforded 4-hydroxytetrahydropyran in excellent yields (95-96%).
Project description:Boron hydride clusters are an extremely diverse compound class, which are of enormous importance to many areas of chemistry. Despite this, stable aluminium hydride analogues of these species have remained staunchly elusive to synthetic chemists. Here, we report that reductions of an amidinato-aluminium(III) hydride complex with magnesium(I) dimers lead to unprecedented examples of stable aluminium(I) hydride complexes, [(ArNacnac)Mg]2[Al6H6(Fiso)2] (ArNacnac?=?[HC(MeCNAr)2]-, Ar?=?C6H2Me3-2,4,6 Mes; C6H3Et2-2,6 Dep or C6H3Me2-2,6 Xyl; Fiso?=?[HC(NDip)2]-, Dip?=?C6H3Pri2-2,6), which crystallographic and computational studies show to possess near neutral, octahedral hypercloso-hexaalane, Al6H6, cluster cores. The electronically delocalised skeletal bonding in these species is compared to that in the classical borane, [B6H6]2-. Thus, the chemistry of classical polyhedral boranes is extended to stable aluminium hydride clusters for the first time.