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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]

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]

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]

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 single-crystal X-ray structure determinations of the title complexes, cis-di­chloro- trans-di­methyl- cis-bis( N-methyl­pyr­rolidin-2-one- O)­tin(IV), [Sn(CH3)2Cl2(C5H9NO)2], cis-di­bromo- trans-di­methyl- cis-bis( N-methyl­pyrrolidin-2-one- O)tin­(IV), [SnBr2(CH3)2(C5H9NO)2], and cis-di­iodo- trans-di­methyl- cis-bis( N-methyl­pyrrolidin-2-one- O)­tin(IV), [Sn(CH3)2I2(C5H9NO)2], show that those tin complexes in which coordination of the lactam ligand to SnIV is realized via oxygen exhibit a distorted octahedral geometry. [ABSTRACT FROM AUTHOR]

The title compound, di-μ-chloro-bis{[(2,3,4-η)-ethyl 6,6-di­methyl-5-oxohept-2-enoato]­palladium(II)}, [Pd2Cl2(C11­H17­O3)2], is a binuclear chloro-bridged palladium allyl complex that was obtained serendipitously From the reaction of 6,6-di­methyl-2-hepten-4-ynoate with Na2PdCl4 in water-containing alcohol. The allyl group is substituted with an ester and a tert-butyl­carboxy group. The dimeric mol­ecules link via C-H⃛O contacts into a two-dimensional network parallel to the bc plane. [ABSTRACT FROM AUTHOR]

Stereoselective hydroboration of (−)-isopulegol and subsequent fractional crystallization furnishes the title compound, C10H20O2. The relative configuration of the stereogenic centres has been assigned by means of X-ray diffraction analysis since the monoterpenediol is employed as a versatile chiral building block in stereospecific natural product synthesis. [ABSTRACT FROM AUTHOR]

Esterification of a single diastereomer of 2-(4-methylene­cyclohex-2-enyl)propanol, (II), with (1 R,4 S)-(+)-camphanic acid [(1 R,4 S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylic acid] leads to the crystalline title compound, C20H28O4. The relative configuration of the camphanate was determined by X-ray diffraction analysis. The outcome clarifies the relative and absolute stereochemistry of the naturally occurring bisabolane sesquiterpenes β-turmerone and β-sesquiphellandrene, since we have converted (II) into both natural products via a stereospecific route. [ABSTRACT FROM AUTHOR]

The preparation and X-ray analysis of the title compound, [Sn2Br4(CH3)4(C5H9NO)], are described. The compound contains two Sn atoms in the asymmetric unit, that complexed by N-methyl­pyrrolidin-2-one being hexacoordinated ( a), the other exhibiting pentacoordination ( b). The most important features are three different Sn-Br bond lengths at both Sn atoms with the following values: ( a) 2.5060 (9), 2.7152 (10) and 3.7118 (10) Å; ( b) 2.5084 (10), 2.5279 (9) and 3.5841 (10) Å. [ABSTRACT FROM AUTHOR]

The synthesis and the X-ray structural analysis of the title compound, μ-chloro-1:2κ2 Cl-tri­chloro-1κ Cl,2κ2 Cl-tetra­methyl-1κ2 C,2κ2 C-( N-methyl­pyrrolidin-2-one)-1κ O-ditin(IV), [Sn2Cl4(CH3)4(C5H9NO)], are described. The title compound is found to exhibit a distorted trigonal-bipyramidal geometry at both SnIV atoms. The Sn-Cl-Sn angle involving the bridging chlorine ligand is 135.56 (5)°, with the Sn-Cl bond lengths being 2.5704 (13) and 3.1159 (13) Å. [ABSTRACT FROM AUTHOR]

The synthesis and X-ray structure analysis of the title compound, [SnBr2(CH3)2(C4H9NO)2], are described. The crystal contains mol­ecules which are separated by normal van der Waals distances. Organotin(IV) compounds are found in a variety of structural types, in which the Sn atom can, for example, be hexacoordinated. In this case, the preferred solid-state molecular structure of the central atom is octahedral. The degree of distortion and the configuration depend on the ligands. [ABSTRACT FROM AUTHOR]

The synthesis and crystal structure analysis via X-ray diffraction of the title compound, C20H24O4, (I), are described. The title compound is an androstadione bearing a diene in the A and B rings [Krause & Thorand (1999). Inorg. Chim. Acta, 296, 1-11]. The diene conjugates with the carbonyl group. Intermolecular H⃛O contacts (2.53 and 2.64 Å; C-H⃛O angles 161 and 158°) indicate hydrogen bonds. [ABSTRACT FROM AUTHOR]

The crystal structure of the title compound, C10H20O2, was published [Körner et al. (2000). Acta Cryst. C 56, 74-75] with an erroneous position for an hydroxy H atom. This has now been corrected and leads to a more sensible hydrogen-bonding scheme. [ABSTRACT FROM AUTHOR]

The synthesis, spectroscopic data and X-ray structural analysis of the title compound, C26H35NO2S, (I), are described. The crystal contains discrete mol­ecules separated by normal van der Waals distances. The benzene­sulfon­amide derivative of the corresponding amine allows the assigment of its relative configuration. The secondary amine has been synthesized via a sequential multi-step hydro­formyl­ation procedure according to Eilbracht et al. [ Chem. Rev. (1999), 99, 3329-3365].). [ABSTRACT FROM AUTHOR]

The title compound, C12H16O4, (I), was prepared by oxidation of (5 S*,6 R*)-1,7-di­oxa­di­spiro­[4.0.4.4]­tetra­decane-2,8-diol us­ing silver(I) carbonate and posesses a cis configuration of the two five-membered-ring lactones fused spiro to the six-membered carbocycle, which has a chair conformation. It represents an exceptional structure for bis-tetra­hydro­furan units, which are interesting building blocks in natural products. The synthesis, spectroscopic data and X-ray structural analysis are described. The crystal contains discrete mol­ecules separated by normal van der Waals distances. [ABSTRACT FROM AUTHOR]

The title compound, C16H26O2, (I), prepared by oxidation of (1 R*,11 R*)-12-hydroxy­bi­cyclo­[9.4.1]­hexa­decan-16-one using pyridinium dichromate, has a trans configuration of the two fused rings and represents an interesting precursor for the synthesis of macrocyclic structures. [ABSTRACT FROM AUTHOR]

The title compound, C23H19N2O3P, was prepared by the reaction of ethynyldi­phenyl­phosphine oxide with phenyl isocyanate, triethyl­amine and nitoethane in benzene. The molecular structure is stabilized by an intramolecular N-H⋯O hydrogen bond. [ABSTRACT FROM AUTHOR]

The title compound, di­bromo­di­methyl( N-methyl­pyrrolidin-2-one- O)­tin(IV), [SnBr2(CH3)2(C5H9NO)], exhibits pentacoordination of the Sn atom, with long and short Sn-Br bonds [2.6737 (4) and 2.5256 (4) Å, respectively]. The distorted trigonal-bipyramidal coordination polyhedron has two methyl groups and one Br atom in the equatorial plane, the second Br atom and the N-methyl­pyrrolidinone (NMP) ligand occupying the apical positions. [ABSTRACT FROM AUTHOR]