Search

We developed an enantioselectively catalyzed tandem synthesis of structurally and stereochemically complex molecules that forms four carbon-carbon bonds and sets eight stereocenters with high regio-, diastereo- and enantioselectivity. It can be programmed to yield different stereoisomers by varying only the order of combination of a common set of reagents and catalysts. We report what is to our knowledge the first synthesis of both enantiomers of a chiral compound using the same chiral catalyst. [ABSTRACT FROM AUTHOR]

The article focuses on the crystallization of the compound tris(cyclohexylmethyl)amine. The compound formed is a sterically hindered amine with three cyclohexane rings having chair conformations. In the experiment a solution of cyclohexene in dioxane, methanol and glacial acetic acid in the presence of urea was treated under hydroaminomethylation conditions. The mixture was extracted with ethyl acetate.

The title compound, C18H29IO3, features a trans-fused bicyclic system. The carbonyl group lies on the same side as the carbethoxy function and iodine. The six-membered ring has a chair conformation. [ABSTRACT FROM AUTHOR]

Summary: Natural products endowed with neuromodulatory activity and their underlying structural scaffolds may inspire the synthesis of novel neurotrophic compound classes. The spirocyclic secoyohimbane alkaloid rhynchophylline is the major component of the extracts of Uncaria species used in Chinese traditional medicine for treatment of disorders of the central nervous system. Based on the structure of rhynchophylline, a highly enantioselective and efficient organocatalyzed synthesis method was developed that gives access to the tetracyclic secoyohimbane scaffold, embodying a quaternary and three tertiary stereogenic centers in a one-pot multistep reaction sequence. Investigation of a collection of the secoyohimbanes in primary rat hippocampal neurons and embryonal stem cell-derived motor neurons led to discovery of compounds that promote neurite outgrowth and influence the complexity of neuronal network formation. [Copyright &y& Elsevier]

The PdII-catalyzed cycloisomerization of 3-alkoxycarbonyl-3-hydroxy-substituted 1,5-hexadienes has been studied experimentally and computationally. Experimentally, the reaction is characterized by a rapid room temperature formation of monomeric as well as dimeric cycloisomerization products using the commercially available precatalyst [(CH3CN)4Pd](BF4)2. In situ NMR measurements indicate the initial kinetic advantage of the desired cycloisomerization pathway to methylene cyclopentanes; however, double bond isomerization, elimination, and dimer formation are competitive undesired pathways. Evaluation of the obtained product structures by NMR spectroscopy and X-ray crystallography indicates that the sole determinant for the monomer/dimer ratio is the regioselectivity of the initial hydropalladation in favor of the allylic (monomer formation) or the homoallylic double bond (dimer formation). In order to account for the experimental results, we propose the coexistence of two product-forming catalytic cycles, an open, monomer generating, as well as an interrupted and redirected, dimer generating, hydropalladation/carbopalladation/β-hydride elimination (HCHe) process. Results from computational studies of the proposed competing catalytic cycles are supportive to our mechanistic hypothesis and pinpoint the pivotal importance of PdII-hydroxo-chelate complexes for the reactivity--stability interplay of on- and off-pathway intermediates. [ABSTRACT FROM AUTHOR]

In biology-oriented synthesis, the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is, in particular, met by the scaffolds of natural products selected in evolution. The synthesis of natural product-inspired compound collections calls for efficient reaction sequences that preferably combine multiple individual transformations in one operation. Here we report the development of a one-pot, twelve-step cascade reaction sequence that includes nine different reactions and two opposing kinds of organocatalysis. The cascade sequence proceeds within 10-30 min and transforms readily available substrates into complex indoloquinolizines that resemble the core tetracyclic scaffold of numerous polycyclic indole alkaloids. Biological investigation of a corresponding focused compound collection revealed modulators of centrosome integrity, termed centrocountins, which caused fragmented and supernumerary centrosomes, chromosome congression defects, multipolar mitotic spindles, acentrosomal spindle poles and multipolar cell division by targeting the centrosome-associated proteins nucleophosmin and Crm1. [ABSTRACT FROM AUTHOR]

The title compound, C25H29NO3, was prepared in the course of the generation of depsipeptide libraries resembling the Jasplakinolide family of natural products. The dihedral angle between the phenyl ring planes is 74.1 (3)° The oxazolidinone ring adopts a slightly distorted 4 E conformation with an axial projection of the isopropyl substituent, which is easily rationalized by pseudo-allylic strain exerted by the exocyclic imide carbonyl. The two carbonyl groups adopt a noncolinear S-shaped conformation. [ABSTRACT FROM AUTHOR]

The molecule of the title compound, C20H34O4, is centrosymmetric. In the crystal structure, a network of O—H...O hydrogen bonds result in each molecule being linked to four neighbouring molecules and a two-dimensional net is formed. [ABSTRACT FROM AUTHOR]

The chiral title compound, C17H20ClNO5, arose as a side product during the synthesis of novel furanomycin derivatives. The stereochemistry at the bicyclic core is consistent with a halolactonization step. The five-membered rings are nearly perpendicular to each other [torsion angle at the common bond: −88.3 (3)°]. [ABSTRACT FROM AUTHOR]

The title compound, C12H15ClF3NO4, is a side product in a synthesis of novel furanomycin derivatives. The stereochemistry at the bicyclic core is consistent with a halolactonization step. However, racemization also occurred via an unknown mechanism. The five-membered rings are nearly perpendicular to each other [torsion angle at the common bond: −95.6 (2)°]. [ABSTRACT FROM AUTHOR]

The title compound, C8H12O3, was synthesized to prove the relative configuration in the projected total synthesis of curvicollides A–C. In the crystal structure, molecules are linked via a bifurcated O—H...O hydrogen bond and a chain of molecules is formed along the a axis. [ABSTRACT FROM AUTHOR]

The title compound, C20H27NO4, is a synthetic inter­mediate towards the preparation of novel furan­omycin derivatives. Its structure is consistent with the assumed anti selectivity of the allenylation step. [ABSTRACT FROM AUTHOR]

Abstract: The pentacyclic spirotryprostatin scaffold embodies an oxindole with an all-carbon quaternary stereocenter. The scaffold can efficiently be accessed in a one-pot reaction sequence consisting of a highly enantioselective 1,3-dipolar cycloaddition, N-acylation of the resulting stereochemically complex 3,3′-pyrrolidinyl-spirooxindole core with Fmoc-proline and spontaneous ring closure upon N-deprotection. [Copyright &y& Elsevier]

In Biology Oriented Synthesis the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is met by the structurally complex scaffolds of natural products (NPs) selected in evolution. The synthesis of NP-inspired compound collections approaching the complexity of NPs calls for the development of efficient synthetic methods. We have developed a one pot 4-7 step synthesis of mono-, bi-, and tricyclic oxepanes that resemble the core scaffolds of numerous NPs with diverse bioactivities. This sequence entails a ring-closing ene-yne metathesis reaction as key step and makes productive use of polymer-immobilized scavenger reagents. Biological profiling of a corresponding focused compound collection in a reporter gene assay monitoring for Wntsignaling modulation revealed active Wntepanes. This unique class of small-molecule activators of the Wnt pathway modulates the van-Gogh-like receptor proteins (Vangl), which were previously identified in noncanonical Wnt signaling, and acts in synergy with the canonical activator, protein (Wnt-3a). [ABSTRACT FROM AUTHOR]

The title compound, C17H32N4, contains two piperazine heterocycles, which are methyl­ene bridged. The rings have chair conformations, with all substituents equatorial. [ABSTRACT FROM AUTHOR]

The title compound, C21H26N2, a potential chiral ligand for transition metal-catalysed reactions, crystallizes with one mol­ecule in the asymmetric unit; the mol­ecule has a pseudo-twofold axis perpendicular to the central C=C=C fragment. [ABSTRACT FROM AUTHOR]

The crystal structure of the title compound, C11H12O, a substrate for gold-catalysed cyclo­isomerization reactions [Hoffmann-Röder & Krause (2001). Org. Lett. 3, 2537–2538], contains two mol­ecules in the asymmetric unit. There are two inter­molecular O—H ⋯ O hydrogen bonds in the crystal structure and a chain of mol­ecules is formed along the c axis via these hydrogen bonds. [ABSTRACT FROM AUTHOR]

In biology-oriented synthesis the underlying scaffold classes of natural products selected in evolution are used to define biologically relevant starting points in chemical structure space for the synthesis of compound collections with focused structural diversity. Here we describe a highly enantioselective synthesis of natural-product-inspired 3,3′-pyrrolidinyl spirooxindoles—which contain an all-carbon quaternary centre and three tertiary stereocentres. This synthesis takes place by means of an asymmetric Lewis acid-catalysed 1,3-dipolar cycloaddition of an azomethine ylide to a substituted 3-methylene-2-oxindole using 1–3 mol% of a chiral catalyst formed from a N,P-ferrocenyl ligand and CuPF6(CH3CN)4. Cellular evaluation has identified a molecule that arrests mitosis, induces multiple microtubule organizing centres and multipolar spindles, causes chromosome congression defects during mitosis and inhibits tubulin regrowth in cells. Our findings support the concept that compound collections based on natural-product-inspired scaffolds constructed with complex stereochemistry will be a rich source of compounds with diverse bioactivity. [ABSTRACT FROM AUTHOR]

The article presents a study on the synthesis of 3-hydroxypyridines with concerted cycloaddition mechanism. The study has demonstrated that highly functionalized 3-hydroxypyridines can be obtained from α,α-dicyanoalkenes 6 with excellent yield, chemoselectivity, and complete regiocontrol. The study's findings can be useful in the exploration of 3-hydroxypyridines in materials, synthesis, and medicinal chemistry.

In the title compound, C14H30O4Si, the bond angles around Si are in the range 105.4 (3)–112.1 (4)° and the tetra­hydro­furan ring adopts a distorted envelope conformation. There is one intra­molecular and one inter­molecular O—H⋯O hydrogen bond in the crystal structure. A spiral of mol­ecules forms around the 41 axis ( c axis) of the crystal structure via the inter­molecular O—H⋯O hydrogen bond. [ABSTRACT FROM AUTHOR]

The title compound, C20H19F3N2O4, crystallizes with two mol­ecules in the asymmetric unit. The important characteristics of the mol­ecule are the two C=N bonds in Z,E configuration, one in the β-methoxy-system and the other in the oxy­methyl side chain between the two aromatic rings. [ABSTRACT FROM AUTHOR]

The crystal structure of the title compound, C20H19F3N2O4, contains one mol­ecule in the asymmetric unit. The CF3 group is disordered over two positions. The important characteristics of the mol­ecule are the two C=N bonds in an E,Z-configuration, viz. E in the β-methoxy system and Z in the oxymethyl chain between the two aromatic rings. [ABSTRACT FROM AUTHOR]

The crystal structure of the title compound, C19H17F3N2O4, a metabolite of the fungicide trifloxy­strobin (TFS), contains one mol­ecule in the asymmetric unit. The CF3 group is disordered over two positions. The important characteristics of the mol­ecule are the two C=N bonds in an E,E configuration, one in the β-methoxy system and the other in the oxy­methyl side chain between the two aromatic rings. The mol­ecules are linked via an O—H⋯N hydrogen bond and an infinite spiral is formed along the b-axis direction. [ABSTRACT FROM AUTHOR]

The chiral title compound, C28H26O2, with potential uses in the synthesis of aza­macroheterocycles, shows a locked S-configuration for the binaphthyl unit. The diolefinic building blocks were prepared as diallylic ethers of ( S)-1,1′-binaphthol. The dihedral angle between the least-squares planes of the bicyclic ring systems is 68.53 (3)°. The mol­ecule resides on a twofold axis. [ABSTRACT FROM AUTHOR]

The chiral title compound, C12H17OP, with potential uses in asymmetric induction in homogeneous catalysed reactions, shows an s- cis conformation for the C=C—P=O unit, in common with related materials. [ABSTRACT FROM AUTHOR]

In the title compound, C40H32N2O2P2, used as a nixantphos-type ligand in homogeneous catalysis, the central phenoxazine ring system deviates markedly from planarity, the dihedral angle between the two halves being 38.14 (3)°. The intra­molecular P⋯P distance is 4.2400 (7) Å. [ABSTRACT FROM AUTHOR]

In the title compound, C40H33NO3P2, used as a nixantphos-type ligand in homogeneous catalysis, the central phenoxazine ring system is nearly planar. The most important feature of the mol­ecule is the intra­molecular P⋯P distance of 4.2346 (13) Å. The angles involving the P atoms are in the range 100.90 (13)–103.40 (16)°. [ABSTRACT FROM AUTHOR]

The title compound, C25H35O3PS, is a chiral phosphinate containing five stereogenic centers, one at the P atom, one at the S atom and three in the (−)-menthyl group. The crystal packing reveals that mol­ecules are linked into chains along the a axis by inter­molecular C—H⋯O hydrogen-bonding inter­actions. [ABSTRACT FROM AUTHOR]

The title compound, C42H41NOP2Si, used as a nixantphos-type ligand in homogeneous catalysis, crystallizes with one mol­ecule in the asymmetric unit. The mol­ecule has nearly mirror symmetry with N, O and Si on the pseudo-mirror plane, but it is not located on a crystallographic mirror plane. The most important feature of the mol­ecule is the intra­molecular P—P distance of 4.1453 (12) Å. The bond angles involving the P atoms are in the range 100.32 (14)–103.04 (15)°. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, (4a R,5 R,6 S,7 S,8a S)-methyl 8a-ethenylocta­hydro-5-acet­oxy-7-{[2-(acetoxy­meth­yl)-1-oxo-2-propen­yl]­oxy}-α,4-bis­(methyl­ene)-3-oxo-1 H-2-benzopyran-6-acetate, C24H28O10, the mol­ecule has a cis configuration at the junction of the two six-membered rings and not a trans configuration as was assigned on the basis of NMR data in solution [Asaka et al. (1977). Phytochemistry, 16, 1838–1839]. [ABSTRACT FROM AUTHOR]

The mol­ecule of the title compound, C16H30O2, features a trans-fused bicyclic system. The six-membered ring has a chair conformation. The mol­ecules are linked via an O—H⋯O hydrogen bond [O⋯O = 2.7696 (11) Å and O—H⋯O = 174.2 (13)°] to form chains along the b axis. An intra­molecular O—H⋯O hydrogen bond [O⋯O = 2.6722 (11) Å and O—H⋯O = 148.4 (13)°] is present. [ABSTRACT FROM AUTHOR]