A two-step telescoped synthesis of 4-vinyl-2,3-dihydrobenzofuran (2) was demonstrated using imidate ester chemistry and phase-transfer catalysis. Treatment of 2,3-bis(2-hydroxyethyl)-phenol (1) with the Vilsmeier reagent resulted in an in situ generation of a bis-imidate intermediate 4, which was converted to 4-(2-chloroethyl)-2,3-dihydrobenzofuran (6) via a sequential ring closure and chloride displacement reactions. Further dehydrobalogenation of 6 using a phase-transfer catalyst provided an excellent, cost-effective method to prepare high quality 4-vinyl-2,3-dihydrobenzofuran (2). The yields for the two-step telescoped process ranged from 83 to 90%.

A practical, safe, and high-yielding process for the cyclopropanation of a chiral epoxide has been developed using the inexpensive and nonhazardous reagents triethylphosphonoacetate and sodium tert-butoxide.

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTA Practical Synthesis of trans-Dichlororuthenium ((S,S)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)- pyridine)(ethylene) Amenable to Large-Scale PreparationMichael J. Totleben, J. Siva Prasad, James H. Simpson, Steven H. Chan, Dale J. Vanyo, Daniel E. Kuehner, Rajendra Deshpande, and Gus A. KodershaView Author Information Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, One Squibb Dr., P.O. Box 191, New Brunswick, New Jersey 08903-0191 [email protected]Cite this: J. Org. Chem. 2001, 66, 3, 1057–1060Publication Date (Web):January 10, 2001Publication History Received18 September 2000Published online10 January 2001Published inissue 1 February 2001https://pubs.acs.org/doi/10.1021/jo005652khttps://doi.org/10.1021/jo005652kbrief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1773Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Anions,Catalysts,Ligands,Mixtures,Separation science Get e-Alerts

Hydrogen-ion titrations were conducted for hen-egg-white lysozyme in solutions of potassium chloride over the range pH 2.5−11.5 and for ionic strengths to 2.0 M. The dependence of lysozyme's net proton charge, zp, on pH and ionic strength in potassium chloride solution is measured. From the ionic-strength dependence of zp, interactions of lysozyme with potassium and chloride ions are calculated using the molecular- thermodynamic theory of Fraaije and Lyklema.1 Lysozyme interacts preferentially with up to 12 chloride ions at pH 2.5. The observed dependence of ion−protein interactions on pH and ionic strength is explained in terms of electric-double-layer theory. New experimental pKa data are reported for 11 amino acids in potassium chloride solutions of ionic strength to 3.0 M.

The diffusion of hen egg-white lysozyme has been studied by dynamic light scattering in aqueous solutions of ammonium sulfate as a function of protein concentration to 30 g/liter. Experiments were conducted under the following conditions: pH 4-7 and ionic strength 0.05-5.0 M. Diffusivity data for ionic strengths up to 0.5 M were interpreted in the context of a two-body interaction model for monomers. From this analysis, two potential-of-mean-force parameters, the effective monomer charge, and the Hamaker constant were obtained. At higher ionic strength, the data were analyzed using a model that describes the diffusion coefficient of a polydisperse system of interacting protein aggregates in terms of an isodesmic, indefinite aggregation equilibrium constant. Data analysis incorporated multicomponent virial and hydrodynamic effects. The resulting equilibrium constants indicate that lysozyme does not aggregate significantly as ionic strength increases, even at salt concentrations near the point of salting-out precipitation.

A molecular-thermodynamic model is developed for salt-induced protein precipitation. The model considers an aqueous solution of a globular protein as a system of interacting hard spheres in a continuum pseudo-solvent (water and salt ions). The protein molecules are considered to interact in a manner described by a set of spherically-symmetric two-body potentials of mean force. These include screened Coulombic repulsion, dispersion (van der Waals) attraction, osmotic attraction, and an attractive square-well potential intended to model specific protein-protein chemical interactions (including the hydrophobic effect and protein self-associations). Following Chiew et al. (1995), an analytical equation of state is derived using the Random Phase Approximation with the hard-sphere fluid as the reference system and a perturbation based on the protein-protein overall potential of mean force. This equation of state provides an expression for the chemical potential of the protein and determines liquid-liquid equilibria. The model is generalized for co-precipitation of several proteins. Experimental single-protein precipitation data are correlated for hen egg-white lysozyme and for α-chymotrypsin in concentrated aqueous solutions of ammonium sulfate.

A mokcukr-thermodynamic model is developid for salt-induced protein precipitation the model considers an aquleous solution of globular protein molecules as a s:ystem of interacting hard spheres in a continuum pseudo-solvent (water and salt ions). l%e protein molecules interact in a manner described by a set of sphericaUy-symmetric two-body potentials of mean force. These include screened CMombic repulsion, dispersion (van der Wads) attraction, and ion-excluded-vohnne osmotic attraction. Specific chemical interactions between proteins (e.g., hydrophobic interactions and self-association) am modekd with a short-range, orientationdependent attractive square-weU potentkd. An analytical equation of state is derived using the Random Phase Approximation with the hard-sphere fluid as the reference system and a perturbation based on the protein-protein overall potential of mean force, while the short-range specific chemical intemction is incorporated through the S/WI’ perturbation theory of associating fluids. This equation of state, similar in form to the well-known van der Waals equation of state, provides an expression for the chemieal potential of the protein and determines liquid-liquid phase equilibria. Critical and spinodal criteria for salt-induced protein precipitation are derived, and the dependence of critical points and protein volubility on model parameters is examined. Salting-out phase-equilibrium data are described for two globular proteins, henegg-white lysozyme and bovine cz-chymotrypsin, in solutions of ammoniurh wdf~ at 25”C. For both proteins, the SAFT parameters M, &,P,and V are correlated from the Iysozyme precipitation data of Coen, et al. (1995). Cikulated Cohn-Edsall slopes relating the protein solubllity to the solution ionic strength are greater than those measured in precipitation experiments with lysozyme and chymotrypsin, indicating that ionic--strengthdependent parameters are required for quantitative application of this modei to these proteins.

This report describes a first attempt to quantify the net charge as a function of solution pH for lysozyme and {alpha}-chymotrypsin at 0.1 M, 1.0 M and 3.0 M ionic strength, (IS). The calculations are based on the residue (titratable group) pK{sub a}`s in the amino-acid sequence of the protein. To determine these pK{sub a}`s, a simple theory was used which assumes that the pK{sub a}`s are independent from each other in the protein and are equal to their pK{sub a} values in free amino-acid solution (Independent-Site Theory, IST). Residue pK{sub a}`s were obtained from amino-acid hydrogen-ion titrations at three different KCl concentrations corresponding to 0.1M, 1.0M and 3.0M ionic strength. After construction of a suitable apparatus, the experimental procedure and data reduction were computerized to perform a large number of titrations. Most measured pK{sub a}`s showed high reproducibility (the difference of pK{sub a} values observed between two experiments was less than 0.05). For IS = 0.1M, observed pK{sub a}`s agreed with literature values to within a few hundredths of a pH unit. Furthermore, the ionic-strength dependence of the pK{sub a}`s followed the trends reported in the literature, viz. pK{sub a} values decrease with increasing ionic strength until they reach a minimum at about IS = 0.5M. At still higher IS, pK{sub a}`s increase as the ionic strength rises to 3M. The known pK{sub a}`s of all titratable groups in a protein were used with the IST to give a first approximation of how the protein net charge varies with pH at high ionic strength. A comparison of the titration curves based on the IST with experimental lysozyme and {alpha}-chymotrypsin titration data indicates acceptable agreement at IS = 0.1M. However, comparison of measured and calculated titration curves at IS = 1M and IS = 3M indicates only quantitative agreement.

include the known physics of protein interactions in aqueous solution. With this in mind, it is crucial to acknowledge that protein precipitation is fundamentally an aggregation process. In order to incorporate aggregation effects into ongoing efforts to model salting out of proteins, it is necessary to quantify the degree of aggregation as a function of solution conditions. Therefore, dynamic light scattering measurements were performed with a well-studied protein, hen-egg-white lysozyme, under several solution conditions.

HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.