Solid-phase synthesis of dihydrovirginiamycin S1, a streptogramin B antibiotic

We describe the first solid-phase synthesis of dihydrovirginiamycin S(1), a member of the streptogramin B family of antibiotics, which are nonribosomal-peptide natural products produced by Streptomyces. These compounds, along with the synergistic group A components, are "last line of defense" antimicrobial agents for the treatment of life-threatening infections such as vancomycin-resistant enterococci. The synthesis features an on-resin cyclization and is designed to allow production of streptogramin B analogues with diversification at positions 1', 1, 2, 3, 4, and 6. Several synthetic challenges known to hinder the synthesis of this class of compounds were solved, including sensitivity to acids and bases, and epimerization and rearrangements, through the judicious choice of deprotection conditions, coupling conditions, and synthetic strategy. This work should enable a better understanding of structure-activity relationships in the streptogramin B compounds, possible identification of analogues that bypass known resistance mechanisms, and perhaps the identification of analogues with novel biological activities.     

Evidence for a trigonal twist mechanism involving a phosphite ligand of Os3(CO)7,[P(OMe)3]5

The fluxional molecule Os₃(CO)₇[P(OMe)₃]₅ has been prepared from OS₃(CO)₁₂ and P(OMe)₃ by a combination of thermal and UV irradiation synthetic methods. An investigation by ³¹P and ¹³C NMR spectroscopy indicated that the mechanism of fluxionality in this compound probably involves the P(OMe)₃ ligand of the Os(CO)₃[P(OMe)₃] unit moving from one equatorial site to the other via a trigonal twist mechanism.     

Light-directed radial combinatorial chemistry: orthogonal safety-catch protecting groups for the synthesis of small molecule microarrays

We describe the development of photolabile protecting groups based on the 3,4,5-trimethoxyphenacyl group (TMP). Orthogonal safety-catches were created by introducing an acid-activatible dimethyl ketal (AA-TMP) and an oxidatively activatible 1,3-dithiane (OA-TMP) into the photolabile TMP group. We demonstrate the application of these protecting groups in light-directed synthesis of small molecule microarrays with diversity elements radially attached to a hydroxyproline scaffold.     

Nucleophilic Addition of CH, NH, and OH Bonds to the Phosphadiazonium Cation and Interpretation of (31)P Chemical Shifts at Dicoordinate Phosphorus Centers

The phosphadiazonium cation [MesNP](+) reacts quantitatively with the fluorenylide anion, MesNH(2), and MesOH (Mes = 2,4,6-tri-tert-butylphenyl), resulting in formal insertion of the N-P moiety into the H-Y (Y = C, N, O) bonds. Specifically, reaction of MesNPCl with fluorenyllithium gives the aminofluorenylidenephosphine [crystal data: C(31)H(38)NP, monoclinic, P2(1)/c, a = 9.568(8) ?, b = 24.25(2) ?, c = 11.77(1) ?, beta = 101.38(8) degrees, Z = 4]. Similarly, reaction of [MesNP][GaCl(4)] with MesNH(2) gives the diaminophosphenium salt [MesN(H)PN(H)Mes][GaCl(4)] [crystal data: C(36)H(60)Cl(4)GaN(2)P, monoclinic, C2/c, a = 24.921(2) ?, b = 10.198(4) ?, c = 16.445(2) ?, beta = 93.32(1) degrees, Z = 4], and reaction with MesOH gives the first example of an aminooxyphosphenium salt [MesN(H)POMes][GaCl(4)]. It is proposed that the reactions involve nucleophilic attack at phosphorus followed by a 1,3-hydrogen migration from Y to N. Experimental evidence for the formation of sigma-complex intermediates is provided by the isolation of [MesNP-PPh(3)][SO(3)CF(3)] [crystal data: C(37)H(44)F(3)NO(3)P(2)S, triclinic, P&onemacr;, a = 10.663(1) ?, b = 19.439(1) ?, c = 10.502(1) ?, alpha = 103.100(7) degrees, beta = 113.311(7) degrees, gamma = 93.401(7) degrees, Z = 2]. As part of the unequivocal characterization of the aminooxyphosphenium salt, detailed solid-state (31)P NMR studies and GIAO calculations on the phosphenium cations have been performed. Contrary to popular belief, the phosphorus shielding in dicoordinate cations is not caused by the positive charge but results from efficient mixing between the phosphorus lone pair and pi orbitals.     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

Complexometric determination of magnesium oxide in flyash blended cement

A complexometric titration method is proposed to determine magnesium oxide in flyash blended cement. A 0.50 g of sample was heated with hydrochloric acid for 10 min. The solution was diluted to 500 ml, and 50 ml was pipetted and heated to boiling with 2.5 ml of 5% ammonium oxalate solution. The solution was then made alkaline by ammonium hydroxide. The suspension was cooled and filtered. The filtrate was titrated by standard 0.002M EDTA solution. The concentration of MgO in sample was calculated. The flyash content of the sample was determined by British Standard method and the recovery factor (f) was calculated by the equation of f = 100/(99 - 0.315 x %FA). Concentration of MgO in sample was corrected by multiplying the recovery factor with concentration initially found by EDTA titration. The precision of the method is better with more time saving than the official methods.     

Probing water interactions and vacancy production on gadolinia-doped ceria surfaces using electron stimulated desorption

Polycrystalline gadolinia-doped ceria (GDC) surfaces were studied using low-energy (5-400 eV) electron stimulated desorption (ESD). H(+), O(+), and H(3)O(+) were the primary cationic desorption products with H(+) as the dominant channel. H(+), H(3)O(+), and O(+) have a 22 eV threshold followed by a yield change around 40 eV. H(+) also has an additional yield change approximately 75 eV and O(+) has an additional change approximately 150 eV. The O(+) ESD yield change approximately 150 eV may indicate bond breaking of Gd-O and the involvement of oxygen vacancies. The H(+) and H(3)O(+) threshold data collectively indicate the presence of hydroxyl groups and chemisorbed water molecules on the GDC surfaces. ESD temperature dependence measurements show that the interaction of water with GDC surface defect sites, mainly oxygen vacancies, influences the desorption of H(+), O(+), and H(3)O(+). The temperature dependence of the O(+) ESD at 400 eV incident electron energy yields a 0.21 eV activation energy. This is close to the energy needed for oxygen vacancy production next to a pair of Ce(3+) on a CeO(2) surface. These results may indicate a correlation between the O(+) ESD yield and oxygen vacancy density on GDC surfaces and a potential correlation of O(+) ESD and GDC ionic conductivity.     

SOLAR SPECTRAL IRRADIANCE IN THE VISIBLE AND INFRARED REGIONS

Abstract— The analytical formulas previously developed for estimating the spectral irradiance reaching the ground in the ultraviolet are extended into the visible and infrared(350–3000 nm). This approach has two distinct features: (1) all physical inputs for calculating the direct irradiance are given in analytical form, and (2) the diffuse spectral irradiance (skylight) is calculated using dimensionless ratios which relate it to the direct irradiance. In common with other approaches, the global spectral irradiance for arbitrary ground reflectivity is calculated from the sum of the direct and diffuse spectral irradiances and a divisor which depends upon the ground and air spectral reflectivities. The global spectral irradiance on a tilted surface may also be calculated in terms of the above quantities and two angles. As in the case of the ultraviolet, the formulas presented are intended for photobiological applications.     

Phthalocyanines and related compounds: XXXVIII. Synthesis of symmetric taurine- and choline-substituted phthalocyanines

Procedures have been developed for the synthesis of a series of metal complexes derived from water-soluble anionic and cationic octa-4,5-carboxyphthalocyanine-taurine and choline conjugates.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 11, 2004, pp. 1907–1911.Original Russian Text Copyright © 2004 by Mikhalenko, Soloveva, Lukyanets.For communication XXXVII, see [1].This revised version was published online in April 2005 with a corrected cover date.     

Phthalocyanines and related compounds: XLII. Synthesis of phenyl-substituted tetraazachlorins and tetraazabacteriochlorins

New oxidation-resistant hexaphenyl-substituted tetramethyltetraazachlorin, its nickel complex, and tetraphenyl-substituted octamethyltetraazabacteriochlorin and octamethyltetraazaisobacteriochlorin nickel complexes were synthesized for the first time by mixed condensation of diphenylm aleonitrile with tetramethylsuccinonitrile in the presence of lithium dimethylaminoethoxide or nickel chloride. The products were characterized by electronic absorption, ¹H NMR, and mass spectra. Mixed condensation of diphenylsuccinonitrile with phthalonitrile in the presence of nickel chloride was found to give nickel complexes of phenylsubstituted benzo-fused tetraazaporphyrins rather than their hydrogenated derivatives.