Alnumycins A2 and A3: new inverse-epimeric pairs stereoisomeric to alnumycin A1

Two new pairs of stereoisomeric alnumycin As, A2 {(2)-(1R,1′RS,4′SR,5′SR)} and A3 {(2)-(1R,1′RS,4′SR,5′RS)}, are described. Similar to alnumycin A1 {(2)-(1R,1′RS,4′RS,5′SR)}, each of these naturally occurring compounds is also a pair of C-1 inverse epimers. The relative configurations of the dioxane ring sidechains were assigned on the basis of ¹H NMR NOE contacts and molecular modeling using density functional theory (DFT) at the M06-2X/6-31G(d) level of theory. The absolute configurations of C-1 and the determination of inverse epimeric relationships were achieved by experimental electronic circular dichroism (ECD) measurements, with both aspects confirmed by using the chiral derivatizing agent (CDA) Mosher′s acid chloride {α-methoxy-α-trifluorophenylacetyl chloride (MTPACl)} to effect enantiodifferentiation. The absolute configurations of the dioxane ring using the CDA could only be effected in the case of alnumycin A1, the results of which were in agreement with previous assignments. The dioxane ring conformational mobility and the likely interaction between the MTPA groups coupled with the structural novelty of the diols in the dioxane ring with respect to CDA analysis precluded an absolute configuration assignment for alnumycins A2 and A3 based on empirical comparisons or by computational analysis of through-space NMR shieldings (TSNMRS) emanating from the phenyl groups of the MTPA moieties.     

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.     

The absolute configuration of peroxisomicines A1 and A2

Peroxisomicine A1 is a potentially antineoplastic compound isolated from the seeds of Karwinskia parvifolia. It is considered as a useful chemotype for the preparation of topoisomerase II targeted anticancer cells. Stereochemically, it is characterized by the presence of two stereocenters and a rotationally hindered and thus likewise stereogenic biaryl axis. In this contribution, the absolute configuration of peroxisomicine A1 and its epimer, peroxisomicine A2, was established by means of a five-step degradative procedure giving the respective R- and S-configured methyl 2-(2′-methyl-5′-oxotetrahydrofuryl)acetates. The configuration of the degradation product was obtained by means of optical rotation, ¹H NMR analysis using a chiral displacement reagent, and by experimental and quantum chemical circular dichroism (CD) investigations. Based on the results obtained here and considering our previous work on the relative configuration at centers versus axis of these compounds, peroxisomicine A1 resulted to be the P,3S,3′S-isomer and peroxisomicine A2 the P,3R,3′S-isomer.     

A new spiro-type limonoid from Azadirachta indica A. Juss

A rare spiro-type limonoid spirodione (1) was isolated from the seeds of Azadirachta indica A. Juss. Its structure was elucidated through analysis of the spectroscopic data including HRESIMS, NMR, etc., and the absolute configurations were assigned by comparison of experimental and TDDFT-calculated ECD spectra. 1 showed moderate activities against Staphylococcus aureus ATCC 25922 and S. epidermidis ATCC 12228 with MICs of 16 and 64?μg/mL, respectively.     

A quantized approach to space-time

Some consequences are traced of a simple approach to the concept of a quantized relativistic space-time. It is assumed that the basic unit of space-time s₀ depends on the rest-mass of the individual particle m₀ and that the location in space-time of the particle cannot be defined more closely than s₀, where s₀ equals h/m₀ic in space coordinates or h/m₀c² in time coordinates. This leads to the same expressions for the uncertainty in space and time, the de Broglie wavelength, basic frequency and energy levels, and phase velocity as in conventional quantum theory but without the need to introduce a physically significant wave function. This avoids the difficulty in accepting a probability explanation for the wave function and the apparently contradictory wave and particle concepts when dealing with interference and detection from large volumes at very low intensities as well as a possible inversion of cause and effect.Interference appears as the segregation of beams into different units of space-time, each with its own selection of quantum numbers n_i of units s₀ along the four axes but with the same total Σn_i. The different beams correspond merely to a (quantized) change of axes.This approach is compared with that involved in the Schrodinger equation, which leads to an extensive wave function, and this must then be “reduced” by an observation or measurement to establish a localized particle. Prior to such a measurement, the nature of the particle, spread in some sense over the wave function raises questions of reality in unobserved objects. No such problems of reality need arise with the concept of quantized space-time, and the observer intervenes only by choosing the framework axes.     

Absolute configurations of griseorhodins A and C

The known antibiotic and cytotoxic compounds griseorhodin A (1) and griseorhodin C (2) were produced in solid culture by Streptomyces puniceus AB10, which was isolated from the leaf-cutter ant Acromyrmex rugosus rugosus. Their absolute configurations were unambiguously established as 6S,6aR,7S,8S and 6R,6aR,7S,8R, respectively, using vibrational circular dichroism (VCD) and density functional theory (DFT) calculations.     

A new domino-Knoevenagel-hetero-Diels-Alder reaction

Various novel 3,5a,6,11b-tetrahydro-2H,5H-chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-2-ones were synthesized in 60-80% yields via domino-Knoevenagel-hetero-Diels-Alder reactions of 4-thioxo-1,3-thiazolidin-2-one with 3,7-dimethyl-6-octenal, 2-allyloxybenzaldehydes and 2-formylphenyl (E)-3-aryl-2-propenoates with base catalysis. The possibility of stereo- and regioselective cycloaddition was investigated.     

A model for transitional plane Couette flow

A simplified model of plane Couette flow is derived by means of a cross-stream (y) Galerkin expansion in terms of trigonometric functions appropriate for idealized stress-free boundary conditions at the plates. A set of partial differential equations is obtained, governing the in-plane (x–z) space-dependence of a velocity field taken in the form: u=U₀(x,z,t)+[1+U₁(x,z,t)]sin(πy/2), v=V₁(x,z,t)cos(πy/2), w=W₀(x,z,t)+W₁(x,z,t)sin(πy/2). Beyond Lorenz-like Waleffe's modeling (Waleffe 1997), this Swift–Hohenberg type of approach is expected to give an access to the microscopic mechanism of spatiotemporal intermittency typical of the transition to turbulence in plane Couette flow (Pomeau 1986, Bergé et al. 1998).     

A CNDO-MO calculation of VCl4

The electronic structure of the tetrahedral molecule VCL₄ is investigated within the CNDO-MO approximations. The metal and ligand valence orbitals, 3d, 4s, 4p; and 3s, 3p; respectively, have been systematically varied in an attempt to minimize the total energy; “optimum” V 4s(χ₄ = 1.10) and 4p(d ³ p ²) orbitals have been established, but V 3d(d ⁿ ) and Cl(-δ) valence orbitals are only seen to favor lower energy for expanded orbitals. Since determining the one-electron molecular orbital level which is occupied by the vanadium lone electron is a major aspect of this investigation, all calculations have been performed in triplicate: calculations assuming the unpaired electron occupies the 3a ₁, 2 _e and 4t ₂ molecular orbital (ground state electronic configurations² A ₁,² E, and² T ₂, respectively). The Hartree-Fock equations have been solved by Roothaan's SCF method for open shells, but off-diagonal multipliers between filled and partly filled molecular orbitals of the same symmetry have been neglected. As a qualitative estimate of the error introduced by this simplification, the pertinent overlap integrals between the eigenfunctions from calculations for the three possible configurations,² A ₁,² E, and² T ₂, are investigated as functions of the component 3d(d ⁿ ) and Cl(-δ) valence orbitals. The overlap integrals from the relevant² A ₁ and² T ₂ calculations are reasonably small, but the neglect of off-diagonal multipliers in calculations on the² E state is found to be a poor approximation. An ordering of the non-filled molecular orbitals in VCl₄ of 4t ₂ < 3a ₁ < 2e < 5t ₂ seems most consistent with the numerous calculations. This suggested ground state electronic configuration of² T ₂ introduces new aspects to the consideration of a (dynamic) Jahn-Teller effect in VCl₄. Experimental data pertinent to the electronic structure of VCl₄ has been briefly summarized, but unfortunately it is inadequate to confirm or deny the present calculations.     

Alternative synthesis of cystothiazole A

Palladium-catalyzed methoxycarbonylation of (−)-(2R,3S)-1-tert-butyldimethylsiloxy-3-methyl-2-methoxypenta-4-yne 9 derived from (2R,3S)-epoxy butanoate 5 gave the acetylenic ester 10, which was treated with MeOH in the presence of Bu₃P to afford selectively (Z)-β-methoxy acrylate congener 11 in 86% yield. Treatment of (Z)-11 with 99.8% enrichment of CDCl₃ followed by consecutive desilylation and oxidation afforded the left-half aldehyde (+)-2. The overall yield (10 steps from 5; 23%) of (+)-2 via the present route was improved in comparison to that (10 steps from 5; 10%) of the previously reported route. By applying the modified Julia's coupling method, selectivity (E/Z=14:1) of the (E)-form (cystothiazole A 1) against the (Z)-form was improved in comparison to the Wittig method (E/Z=4:1 to 6.9:1).     

A convergent and stereoselective synthesis of a seco-precursor of macrolactin A

A seco-precursor of macrolactin A was synthesized by coupling two advanced segments. Wittig reaction and Horner-Emmons reaction were utilized to construct the three characteristic E,Z and E,E dienes. The C₁-C₁₀ segment was synthesized through Horner-Emmons reaction with phosphonate reagent. The α-alkylation of sulfone stabilized anion with allyl bromide followed by desulfonation gave the C₁₁-C₂₄ segment.     

A sorbent concentration-dependent Freundlich isotherm

During study of the adsorption isotherms at solid–liquid interfaces, a sorbent concentration effect (C _s-effect) phenomenon was observed. In order to describe the C _s-effect, we proposed a new adsorption model, i.e., surface component activity (SCA) model. It supposes that the interaction between the sorbent particles exists in the real adsorption system, which induces the deviation of a real adsorption system from an ideal one. It is the deviation that induces the emerging of the C _s-effect. Based on the SCA model, the activity coefficient of adsorption sites should be a function of the sorbent concentration (C _s), and a C _s-dependent Freundlich equation (Freundlich-SCA equation) was derived. It was confirmed that the Freundlich-SCA equation can describe the C _s-effect observed in adsorption experiments. Its parameters (n _S and K _S) can be simulated with experimental adsorption data and are independent of C _s. Thus, these parameters obtained at given C _s values can be used to predict the adsorption behavior of the adsorbate at any C _s value.     

A carboranylpentaphenylbenzene

1-(o-Carboran-9-yl)-2,3,4,5,6-pentaphenylbenzene (1) was prepared by the Diels-Alder reaction of 9-phenylethynyl-o-carborane and tetraphenylcyclopentadienone at 300 °C. An X-ray crystal structure of 1 shows that the steric demands of the carborane induce a significant stretching of the aryl carbon-boron bond as well as a variety of distortions of the central benzene ring, the ortho phenyl groups, and the carborane cage.     

A different approach to X-ray stress analysis

A different approach to X-ray stress analysis has been developed. At the outset, it must be noted that the material to be analyzed is assumed homogeneous and isotropic. If a sphere with radius r within a specimen is subjected to a state of stress, the sphere is deformed into an ellipsoid. The semi-axes of the ellipsoid have the values of (r + ε_x), (r + ε_y), and (r + ε_z), which are replaced by d_x, d_y, and d_z, or for the cubic case, a_x, a_y, and a_z. In this technique, at a particular ϕ angle (see Fig. 1), the two-theta position of a high angle (hkl) peak is determined at ψ angles of 0, 15, 30, and 45°. These measurements are repeated for 3 to 6 ϕ angles in steps of 30°. The d_ϕψ or a_ϕψ values are then determined from the peak positions. The data is then fitted to the general quadratic equation for an ellipsoid by the method of least squares. From the coefficients of the quadratic equation, the angle between the laboratory and the specimen coordinates (direction of the principle stress) can be determined. Applying the general rotation of axes equations to the quadratic, the equation of the ellipse in the x–y plane is determined. The a_x, a_y, and a_z values for the principal axes of the lattice parameter ellipsoid are then evaluated. It is then possible to determine the unstressed a₀ value from Hooke's Law using a_x, a_y, and a_z. The magnitude of the principal strains/stresses is then determined.     

A crystal chemical study of stishovite

The crystal structure of stishovite, SiO₂, a = 4.1773(1), c = 2.6655(1)Å, space group $\text{P4}{}_2\text{mnm}$, with Z = 2, has been refined with 217 graphite-monochromatized MoKα data (2θ max = 120°) to R = 0.012 (R_w = 0.014). Electron deformation density maps show a modest accumulation of charge density ascribed to partial covalent bonding in both the equatorial and axial bonds together with a delocalization of density in and around the shared octahedron edges with the shorter equatorial bonds showing higher peaks (0.47 eÅ^?3) than the longer axial bonds (0.29 eÅ^?3). Net atomic charges for Si and O determined by a population and κ refinement by varying the occupancy and shape of their valence shells are +1.71 and ?0.86(15) e, respectively. The observed structural distortions and charge distributions conform with the results of ab initio molecular orbital calculations undertaken on molecules designed to mimic the local geometry of the structure of stishovite. The SiO bond length (1.73 Å) calculated for a neutral molecule with 6-coordinated Si is slightly shorter than that observed on the average (1.76 Å) for silicates and molecular crystals with 6-coordinated Si. In addition, the calculated geometrical parameters of two edge-sharing octahedra agree to within ～5% of the observed geometry of stishovite. The calculated charge on Si is indicated to increase with coordination number and bond length in agreement with the larger net charge recorded for stishovite as compared with that recorded for α-quartz, Q(Si) = +1.0 e. Observed deformation maps are compared with theoretical ones calculated in the equatorial plane of the 6-coordinated molecule using molecular orbital theory with a split valence s,p basis supplemented with d-type polarization functions on Si.     

A simple sum rule in raman theory

It is shown that in the limit of large detuning energy and in the absence of coordinate dependence of the transition moment, the resonance Raman amplitude for a 0 → n transition on a harmonic potential surface is proportional to (δ²_? + δ²₊)^?1 × ?^∞_?∞ exp (?q²) · [?ⁿΔV(q)/?q¹¹] dq< where ΔV(q) is the difference between the arbitrary excited-state surface and the initial harmonic potential. The resonant and non-resonant detuning energies are given by δ_? = E ? hv and δ₊ = E + hv, where v is the incident laser frequency and E is the minimum separation between the potential surfaces.     

The biocatalytic conversion of 8-hydroxymanzamine A to manzamine A

The selective dehydroxylation of 8-hydroxymanzamine A (1) to form manzamine A (2) can be completed by fermentation with Fusarium solani or Streptomyces seokies. This unique biocatalytic conversion is important due to the fact that manzamine A has more desirable biological activity when assayed in a murine model against malaria.     

A synthesis of 2-fluoroglucal derivatives

3,4,6-Tri-O-methyl-d-glucal, readily prepared from 3,4,6-tri-O-acetyl-d-glucal, undergoes lithiation at −78 °C in THF with t-BuLi to afford a vinyl carbanion, which can be trapped with electrophiles in moderate overall yields. The palladium coupling and Dötz-type reactions of these intermediates are also described.     

A structural study of ternary lanthanide orthoscandate perovskites

Ternary lanthanide scandates (Ln=La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, and Ho) have been synthesized at ambient pressure. Their structure has been investigated at room temperature by Rietveld analysis of powder X-ray diffraction data. The Ln-scandates are orthorhombic perovskites, adopting space group Pbnm (? 62), a≈b≈√2a_p, c≈2a_p, Z=4. Heavy lanthanides (Er-Lu), and Y do not form perovskites at ambient conditions. Compositionally driven phase transitions were not observed. The unit-cell parameters decrease with increasing ScO₆ octahedron rotation and atomic number of the Ln cation. In common with lanthanide orthoferrites, the uniform structural evolution is interrupted at the middle-heavy part of the lanthanide sequence. This is probably due to an interplay between: (i) enlargement of the ScO₆ octahedra relative to BO₆ in other perovskites (e.g., FeO₆ in GdFeO₃); (ii) reduction in size of the first coordination sphere of Ln³⁺ coincident with the lanthanide contraction; (iii) coincident expansion of the second coordination sphere due to screening effects of O^I1 on O^I2, and entry of Sc to the lanthanide coordination sphere; (iv) complex mixing between oxygen and lanthanide lanthanide f- and scandium d-orbitals. In the series studied, Ln³⁺ are in eight-fold coordination (tetragonal antiprism), and are considerably displaced from the center of the LnO₈ polyhedron along [001]. Evolution of the crystallochemical characteristics through the Ln orthoscandate series is complex due to both the antipathetic distortions of A- and B-site coordination polyhedra and interaction of the orbitals of oxygen, Ln and Sc. Empirically obtained limits of Goldschmidt and observed ^viiit_o tolerance factors for ternary LnBO₃ compounds adopting the Pbnm structure are 0.795 and 0.841, respectively.