Search

SummaryNatural 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.

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.

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.

Triorganotin, triorganolead and tetraphenylantimony derivatives of acetylenedicarboxylic acid (H2ADC), terephthalic acid (H2TER) and dithioterephthalic acid (H2DTT) (R3M)2X (M = Sn, Pb; R = Me, Ph; X = ADC, TER, DTT) and (Ph4Sb)2X (X = ADC, TER) were prepared by neutralization of R3MOH or Ph4SbOH with the appropriate acid (X = ADC, DTT) or by reaction of R3MCl or Ph4SbCl with K2TER. The crystal structures of (Me3Sn)2ADC and (Me3Sn)2TER were determined by X-ray diffraction. The Sn atoms are in slightly distorted trigonal-bipyramidal environments, with C(Me) in the equatorial plane and O(carboxyl) in apical positions. The carboxylate groups are bridging, leading to the formation of a two-dimensional polymer of puckered 22-membered [(Me3Sn)2ADC] and 26-membered [(Me3Sn)2TER] rings. From vibrational spectra, analogous structures are inferred for solid (Ph3Sn)2ADC, (R3Pb)2ADC (R = Me, Ph), and (Me3Pb)2TER, but structures with unidentate - COO and - COS groups and tetracoordinated Sn or Pb and pentacoordinated Sb are proposed for the other compounds. The DTT ligands are linked by S bonds to M. According to IR and 1H NMR studies the polymeric species dissociate on dissolution so that generally species with unidentate carboxylate groups are present. Sn and Pb in (R3M)2X (X = ADC, TER) are apparently tetracoordinated in CHCl3, but pentacoordinated in DMSO by addition of a solvent molecule.

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 CuPF(6)(CH(3)CN)(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.

The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding β-keto aldehyde. In the U-shaped mol­ecule, the five-membered ring approximates an envelope, with the methyl­ene C atom adjacent to the quaternary C atom being the flap, and the methyl and isopropyl substituents lying to the same side of the ring. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 35.74 (15) and 55.72 (9)°, respectively. The bond angles around the S atom are in the range from 103.26 (12) to 120.65 (14)°. In the crystal, mol­ecules are linked via N—H⋯O hydrogen bonds, forming a chain along the a axis.

The title hydrate, C17H28O2·H2O, was synthesized in order to determine the relative configuration of the tetracyclic framework. The fused 5,6,7-tricarbocyclic core exhibits an entirecis-annulation, featuring a 1,4-cis-relation of the angular methyl groups in the six-membered ring. The oxa bridge of the epoxycycloheptane moiety is oriented towards the concave face of the boat-shaped molecule, whereas the angular methyl groups are directed towards the convex face. The asymmetric unit of the crystal contains two nearly identical formula units, which are relatedviaa pseudo-centre of symmetry. The structure could be solved in the space groupsI-4 andI41/a. The refinement in the acentric space group, however, gave significantly better results and these are used in this paper. O—H...O hydrogen bonds are observed between the organic molecules, between the organic molecules and the water molecules, and between the water molecules, forming a chain along thec-axis direction.

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.

Die Darstellung einer Reihe von Dichlor ammoniumsalzen des Typs CH3S(O)2NCl2X+MF6− (X = CH3, Cl, F; M = As, Sb) wird angegeben. Die Salze werden durch oxidative Halogenierung bzw. Methylierung von CH3S(O)2NCl2 erhalten. Die Charakterisierung der thermolabilen Verbindungen erfolgte mittels IR-, Raman-sowie Multikern-NMR-Spektroskopie. Die Einkristallrontgenstrukturanalyse von N,N-Dichlormethylsulfonamid CH3S(O)2NCl2 bei 173(1) K ergab: orthorhombische Raum gruppe Pnma mit a = 615,1(3) pm, b = 937,3(5) pm, c = 970,3(5) pm und Z = 4. New N,N-Dichloromethylsulfonammonium Salts CH3S(O)2NCl2X+MF6− (X = CH3, Cl, F; M = As, Sb) and Crystal Structure of CH3S(O)2NCl2 The preparations of new dichlorammonium salts CH3S(O)2NCl2X+MF6− (X = CH3, Cl, F; M = As, Sb) and of CH3S(O)2NCl2 by oxidative halogenation respectively methylation are reported. The thermolabil compounds are characterized by IR, Raman, 1H, 13C, 19F NMR spectroscopy. N,N-Dichlormethylsulfonamid CH3S(O)2NCl2 crystallizes at 173(1) K in the orthorhombic space group Pnma with a = 615.1(3) pm, b = 937.3(5) pm, c = 970.3(5) pm and Z = 4.

The crystal structure of CH3C6H4S(O)2NCl2 is reported. Crystals are monoclinic, space group P21/c, with a = 710.0(7), b = 1615.3(13), c = 867.2(7) pm, V = 988(2) pm3 and Z = 4. The reaction with HF/SbF5 yields CH3C6H4S(O)2NCl2H+SbF- 6 the first protonated dichloroamine salt, its vibrational -and NMR spectra are discussed

The reaction of Trifluoronitrosomethan with (CH3)2NS(O)2NH2 in THF and Na2CO3 as

The synthesis of salts of the type RnSH3-n +MF6 - (R = C2H5, i-C3H7; n = 1, 2; M = As, Sb) by protonation of the corresponding thiols and sulfides in the superacid systems HF/MF5 is reported. The salts have been characterized by vibrational and NMR spectroscopic methods. Isopropylsulfonium hexafluoroantimonate is the first known example of a sulfonium salt, for which a SH bond distance has been determined by a crystal structure analysis, i-C3H7SH2 +SbF6 - crystallizes in the monoclinic space group P21/m with a = 568.0(4), b = 801.1(6), c = 1019.7(8) pm, β = 82.63(6) °, with two formula units per unit cell.

CH3S(0)C1 reacts in HF as solvent with MF5 (M = As, Sb) to give products CH3S(Cl)OMF5 (M = As, Sb). The new compounds are stable below 253 K and were charac­ terized by Raman and NMR spectroscopy. In addition, the crystal structure of CH3S(Cl)OSbCl5 has been determinated. The complex crystallizes in the monoclinic space group P21/n with a = 644.3(5), b = 1905.9(14), c = 900.0(7) pm, β = 99.27(6)° with four formula units per unit cell.

The investigated crystal of the title compound, C21H34O4, contains two mol­ecules in the asymmetric unit. One mol­ecule shows disorder for two atoms in the 12-membered ring. The two independent mol­ecules show only slight conformational differences. Four mol­ecules are linked via two O—H⋯O hydrogen bonds [O⋯O = 2.816 (2) A and O—H⋯O = 163°; O⋯O = 2.764 (2) A and O—H⋯O = 163°] and a centrosymmetric 16-membered heterocycle containing four hydrogen bonds is formed.

Es wird die Darstellung und spektroskopische Charakterisierung von Dialkylchlorsulfoniumhexachloroantimonaten R2SCl+SbCl6− (R = C2H5, i-C3H7), sowie die Einkristallrontgenstrukturanalyse von Diethylchlorsulfoniumhexachloroantimonat (C2H5)2SCl+SbCl6− bei 172(1) K beschrieben. Das Salz kristallisiert in der orthorhombischen Raumgruppe P212121 mit a = 980,4(13) pm, b = 1010,6(8) pm, c = 1492,8(14) pm mit 4 Formeleinheiten pro Elementarzelle. New Alkylchlorosulfonium Salts and Crystal Structure of Diethylchlorosulfonium-Hexachloroantimonate (C2H5)2SCl+SbCl6− We describe the preparation and spectroscopic characterization of Dialkylchlorosulfonium-Hexachloroantimonates R2SCl+SbCl6− (R = C2H5, i-C3H7) and the crystal structure of Diethylchlorosulfonium-Hexachloroantimonate (C2H5)2SCl+SbCl6− at 172(1) K. The salt crystallize in the orthorhombic space group P212121 with a = 980.4(13) pm, b = 1010.6(8) pm, c = 1492.8(14) pm with four formula units per unit cell.

Es wird die Darstellung von Trifluormethyliodtetrafluorid (CF3IF4), aus Trifluormethyliodid (CF3I) und Trifluormethylhypochlorit (CF3OCl), sowie die Kristallstrukturanalyse bei 172(1) K beschrieben. CF3IF4 kristallsiert in der monoklinen Raumgruppe P21/c mit a = 762,2(7) pm, b = 842,9(10) pm, c = 856,4(7) pm, β = 99,65(7), Z = 4. Fluorinate with Trifluoromethylhypochlorite CF3OCl. Preparation and Crystal Structure Determination of Trifluoromethyliodine Tetrafluoride CF3IF4 The preparation of Trifluoromethyliodine tetrafluoride (CF3IF4), from Trifluoromethyliodide (CF3I) with Trifluoromethylhypochlorite (CF3OCl), and the crystal structure of CF3IF4 at 172(1) K is described. CF3IF4 crystallizes in the monoclinic space group P21/c with a = 762.2(7) pm, b = 842.9(10) pm, c = 856.4(7) pm, β = 99.65(7)° with four formula units per unit cell.

The asymmetric unit of the title compound, C18H30O4, contains two formula mol­ecules, which are described as trans-fused bicyclic systems. The carbonyl group lies on the same side as the carbethoxy function, while the OH group is on the opposite side. The six-membered rings have chair conformations and the conform­ations of the 12-membered rings are similar in the two molecules.

The Pd(II)-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 [(CH(3)CN)(4)Pd](BF(4))(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 Pd(II)-hydroxo-chelate complexes for the reactivity-stability interplay of on- and off-pathway intermediates.

Catalytic enantioselective cycloaddition of azomethine ylides (II) to methylene oxindoles (I) gives pyrrolidinyl-spirooxindoles after acylation with high diastereoselectivity in most cases with exception of ortho-substituted azomethine ylides.

The title compound, C19H24ClNO5, was synthesized and subsequently employed in an Evans alkylation. The purpose was to prove the absolute configuration in the projected synthesis of the side chain of (–)-Lytophilippine A. The oxazolidinone and the isopropylidene acetal rings have twisted conformations. The oxazolidinone and side-chain carbonyl groups are orientated in an antiperiplanar arrangement to minimize van der Waals repulsions. Furthermore, the Cl atom and the acetonide-protected secondary alcohol are also in an antiperiplanar arrangement with a torsion angle of 173.64 (14)°. The absolute configuration was determined and agrees with the configuration of the used chiral auxiliary.

Diorganotin(IV) derivatives of 2-mercaptopyridine (HSPy), R2Sn(SPy)2, R2SnCl(SPy) (R = Me, iPr, nBu, tBu, Cy, Ph) and Cy2SnBr(SPy), were obtained from R2SnX2 (X = Cl, Br) and NaSPy. Ph2SnCl(SPy) crystals, as determined by singlecrystal X–ray diffraction, are monoclinic in the space group P21/n. Tin forms with the bidentate SPy ligand a four–membered chelate ring with a short NSnS bite angle of 64.8(1)° leading to a heavily distorted trigonal–bipyramidal environment about tin. Apical Cl–Sn–N angle = 156.1(1)° equatorial C–Sn–C angle = 121.9(2)°. From 119Sn Mossbauer and IR data, analogous structures are inferred for the other solid compounds R2SnX(SPy), and distorted octahedral molecular structures for the solid compounds R2Sn(SPy)2 with R in the trans position, and sulfur atoms and nitrogen–donor atoms each in cis positions. According to IR and 1H, 13C and 119Sn NMR data, the solid–state molecular structures are retained in chloroform solution.

Es wird uber die Darstellung der Bis(triphenylsilyl)-sulfane Ph3SiSxSiPh3 (x = 3, 4) aus Ph3SiSNa und SCl2 bzw. S2Cl2 berichtet. Ihre Charakterisierung erfolgt schwingungs-, NMR-, und UV-VIS-spektroskopisch. Ph3SiS4SiPh3 kristallisiert in der Raumgruppe P1 mit a = 943,6(6) pm, b = 945,7(5) pm, c = 1 881,7(12) pm, α = 82,11(5)°, β = 78,95(5)°, γ = 83,15(5)° und Z = 2. On the Preparation of Bis(triphenylsilyl)sulfanes (C6H5)3SiSxSi(C6H5)3 (x = 3, 4) and the Crystal Structure of (C6H5)3SiS4Si(C6H5)3 The preparation of the bis(triphenylsilyl)sulfanes Ph3SiSxSiPh3 (x = 3, 4) from Ph3SiSNa and SCl2 resp. S2Cl2 is reported. They are characterized by vibrational, NMR and UV-VIS spectroscopic measurements. Ph3SiS4SiPh3 crystallizes in space group P1 with a = 943.6(6) pm, b = 945.7(5) pm, c = 1 881.7(12) pm, α = 82.11(5)°, β = 78.95(5)°, γ = 83.15(5)° and Z = 2.

Die oxidative Fluorierung der 1,3-Dithiethan-1,1-dioxide (CF3)(R) (R = CF3, Cl) mit XeF+MF6− (M = As, Sb) in wasserfreiem HF fuhrt zur Bildung von Monofluorsulfoniumhexafluorometallaten. Die Salze werden schwingungs-, NMR- und massenspektroskopisch charakterisiert. (CF3)(Cl)F+ AsF6− kristallisiert monoklin in der Raumgruppe P21/c mit a = 9,955(10) A, b = 11,050(5) A, c = 12,733(15) A, β = 97,77(5)° und Z = 4. Oxidative Fluorination of (CF3)(R)(R = CF3, Cl) and the Crystal Structure of (CF3)(Cl)F+ AsF6− Oxidative fluorination of (CF3)(R) (R = CF3, Cl) with XeF+MF6− (M = As, Sb) in anhydrous HF results in formation of monofluorsulfonium hexafluorometalates. The salts are characterized by vibrational, NMR, and mass spectra. (CF3)(Cl)F+ AsF6− crystallizes in the monoclinic space group P21/c with a = 9.955(10) A, b = 11.050(5) A, c = 12.733(15) A, β = 97.77(5)°, and Z = 4.

Die Reaktion von HCl mit einer HF/SbF5 Losung ergibt bei −78°C H2F+SbClF5−. Bei −40°C wird die Bildung von SbCl3F2 beobachtet. Es kristallisiert in der tetragonalen Raumgruppe I-4 mit a = 1 281,6(5) pm, c = 758,1(6) pm und Z = 8. Die Struktur enthalt cis-Fluor-verbruckte Tetramere, in denen Antimon eine verzerrt oktaedrische Koordinationssphare hat. On the Reaction of HCl with HF/SbF5 and the Crystal Structure of SbCl3F2 The reaction of HCl in HF/SbF5 solution at −78°C yields H2F+SbClF5−. At −40°C formation of SbCl3F2 was observed, which crystallizes in the tetragonal space group I-4 with a = 1 281.6(5) pm, c = 758.1(6) pm with 8 formula units per unit cell. The structure contains cis-fluorine-bridged tetramers, in which Sb has a distorted octahedral coordination.

Es wird uber die Darstellung der μ-Schwefeldisulfoniumsalze [(CH3)2SSxS(CH3)2]2+ (A−)2 mit x = 1–3 und A− = AsF6−, SbF6−, SbCl6− berichtet. Die Salze werden durch Kondensationsreaktionen von (CH3)2SH+A− und (CH3)2SSH+A− mit SCl2 bzw. S2Cl2 gebildet. Ihre Charakterisierung erfolgt schwingungsspektroskopisch. Das [(CH3)2SS2S(CH3)2]2+(SbF6−)2 kristallisiert in der Raumgruppe C2/c mit a = 1 884,5(7) pm, b = 1 302,8(5) pm, c = 1 477,2(5) pm, β = 98,62(3)° und Z = 8. Preparation of μ-Sulfurdisulfonium Salts [(CH3)2SSxS(CH3)2]2+2A− (x = 1–3, A− = AsF6−, SbF6−, SbCl6−). On the Analogy of the Reactivity of Sulfanes and Sulfonium Salts The preparation of the μ-sulfurdisulfonium salts [(CH3)2SSxS(CH3)2]2+(A−)2 with x = 1–3 and A− = AsF6−, SbF6−, SbCl6− is reported. The salts are formed by reaction of (CH3)2SH+A− and (CH3)2SSH+A− with SCl2 and S2Cl2, resp. They are characterized by vibrational spectroscopic measurements. [(CH3)2SS2S(CH3)2]2+(SbF6−)2 crystallizes in the space group C2/c with a = 1 884.5(7) pm, b = 1 302.8(5) pm, c = 1 477.2(5) pm, β = 98.62(3)° und Z = 8.

(CF 3 ) 2 NH 2 + MF 6 - (M=As, Sb) were prepared by protonation of (CF 3 ) 2 NH in superacid media and characterized by infrared, Raman, and NMR spectroscopy. (CF 3 ) 2 NH 2 - AsF 6 - crystallizes in the orthorhombic space group Pmcn, with a=7.569 (5) A, b=9.031(6) A, v=13.011(9) A, and Z=4. In the crystal, cation and anion reside on the mirror planes at x=0.25 and x=0.75 of the unit cell, with C-N bond lengths of 1.484(9) and 1.457(9) A, respectively, and an N-H distance of 0.99(7) A

Es wird uber eine einfache Darstellung von CH3PF2 aus CH3PCl2 berichtet, welches in den supersauren Systemen HF/MF5 (M = As, Sb) zu den Phosphoniumsalzen CH3PF2H+MF6− protoniert wird. CH3PF2H+AsF6− kristallisiert in der Raumgruppe P1 mit a = 548,4(4) pm, b = 695,5(8) pm, c = 960,2(9) pm, α = 94,68(5)°, β = 97,19(6)°, γ = 94,41(6)° und Z = 2, das isostrukturelle CH3PF2H+SbF6− mit a = 554,3(3), b = 724,2(4), c = 970,4(5), α = 94,73(4)°, β = 96,14(5)°, γ = 95,30(4)°. On the Crystal Structures of CH3PF2H+AsF6− and CH3PF2H+SbF6− and a simple Method for Preparation of CH3PF2 A simple method for preparation of CH3PF2 from CH3PCl2 is reported. The phosphonium salts CH3PF2H+MF6− are obtained by the reaction of CH3PCl2 with superacidic systems HF/MF5 (M = As, Sb). CH3PF2H+SbF6− crystallizes in the space group P1 with a = 548.4(4) pm, b = 695.5(8) pm, c = 960.2(9) pm, α = 94.68(5)°, β = 97.19(6)°, γ = 94.41(6)° and Z = 2. CH3PF2H+SbF6− crystallizes in P1 with a = 554.3(3), b = 724.2(4), c = 970.4(5), α = 94.73(4)°, β = 96.14(5)°, γ = 95.30(4)°.

The crystal structure of SbCl4F is reported. SbCl4F crystallizes in the tetragonal space group I 4̄ with a = 1278.4(6), c = 774.1(5) pm, V = 1265(1) • 106 pm3 and Z = 8. Four SbCl4F units are linked via symmetric Sb-F-contacts forming an eight-membered heterocycles.