Influence des interactions attractives non liees sur les stabilites relatives d'ethers et d'acetates d'enol renfermant un groupe styryle

The measure of relative stabilities of β-alcoxystyrene isomers I: C₆H₅-CHCH-OR shows that the trans compound is the most stable when RCH₃ and C₂H₅ and the cis compound is the most stable when Ri-C₃H₇ and t-C₄H₉. The orientation of the OR group can be determined by RMN ¹³C. The stabilities of these molecules are discussed in terms of non bounded attractive interactions. This interpretation is confirmed by the measure of relative stabilities of α-methyl β-alcoxy (and acetoxy)-styrene isomers II: C₆H₅-C(CH3)CH-OR. (RCH₃, C₂H₅ et COCH₃).     

Penicillin biosynthesis: Retention of configuration at c-3 of valine during its incorporation into the arnstein tripeptide

[3-³H]-valine was efficiently synthesised from sodium α-ketoisovalerate. With a β-lactam negative mutant of C. acremonium, l-[1-¹⁴C-3-³H]-valine and dl-[1-¹⁴C-3-³H]-valine were independently incorporated into the Arnstein tripeptide dimer, i.e. Bis-δ-(l-α-aminodipyl)-l-cystinyl-bis-d-valine, with full retention of trieium at C-3 of the d-valine residue. This result strongly suggested retention of configuration at C-3 of valine when the tripeptide was biosynthesised, and further limited the number of possible mechanisms for the biosynthesis of penicillins.     

Ribosomal synthesis of unnatural peptides

Combinatorial libraries of non-biological polymers and drug-like peptides could in principle be synthesized from unnatural amino acids by exploiting the broad substrate specificity of the ribosome. The ribosomal synthesis of such libraries would allow rare functional molecules to be identified using technologies developed for the in vitro selection of peptides and proteins. Here, we use a reconstituted E. coli translation system to simultaneously re-assign 35 of the 61 sense codons to 12 unnatural amino acid analogues. This reprogrammed genetic code was used to direct the synthesis of a single peptide containing 10 different unnatural amino acids. This system is compatible with mRNA-display, enabling the synthesis of unnatural peptide libraries of 10(14) unique members for the in vitro selection of functional unnatural molecules. We also show that the chemical space sampled by these libraries can be expanded using mutant aminoacyl-tRNA synthetases for the incorporation of additional unnatural amino acids or by the specific posttranslational chemical derivitization of reactive groups with small molecules. This system represents a first step toward a platform for the synthesis by enzymatic tRNA aminoacylation and ribosomal translation of cyclic peptides comprised of unnatural amino acids that are similar to the nonribosomal peptides.     

Reactions of metal ions with dithizone in molten naphthalene

A comparative study has been made of the reactions of metal ions with dithizone in the two media, chloroform and molten naphthalene. The absorption spectra of several metal dithizonates, prepared in molten naphthalene, were recorded and were found to be the same as those of the dithizonates obtained by extraction of metal ions from aqueous solution with chloroform dithizone.     

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1, ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.     

SIMULTANEOUS MEASUREMENT OF ACTION SPECTRA FOR PHOTOREACTIONS I AND II OF PHOTOSYNTHESIS

Abstract— We have devised a method of obtaining simultaneous action spectra for photoreactions I and II by analysis of direct and indirect effects involved in enhancement. The method requires previous determination of the neutral wavelength which gives maximum quantum yield by virtue of equal fractions of open reaction centers ( p and q ) for each photoreaction. A sufficient intensity of the neutral wavelength is used as a constant background. Upon addition of a weak modulated measuring light of intensity I_m and wavelength λ _m two amperometric signals are obtained for rate of oxygen evolution. A modulated signal (AC¯) isolates the direct effect of I_m and gives action of photoreaction II as AC/ I_m . An increment in total rate (ΔDC) also includes an indirect effect of I_m in perturbing reaction center conditions ( p and q ). From analysis of interaction of the two photoreactions, action for photoreaction I can be estimated as (2 ΔDC-AC)/ I_m . The method is applicable to whole cells, properly scales the two action spectra to each other, and removes contribution of the State 1-State 2 phenomena. Action spectra were obtained for Chlorella.     

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

Three standardised, capillary zone electrophoresis-electrospray ionisation mass spectrometry (CZE-ESI-MS) methods were developed for the analysis of six drug candidates and their respective process-related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected background electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 mM ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE-ESI-MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process-related impurities and provided orthogonality with four established high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings.     

1,4-Difluoro-2,5-dimethoxybenzene as a precursor for iterative double benzyne-furan Diels-Alder reactions

[reaction: see text] The use of 1,4-difluoro-2,5-dimethoxybenzene as a novel precursor for iterative two-directional benzyne-furan Diels-Alder reactions, using a range of 2- and 3-substituted furans, is reported. Substituted oxabenzonorbornadienes were synthesized following the initial Diels-Alder reaction, which upon ring opening under acidic conditions gave substituted naphthol derivatives. Highly substituted anthracenols were generated in the second benzyne-furan Diels-Alder reaction following acid-catalyzed isomerization of the cycloadducts.     

JACOB: An enterprise framework for computational chemistry

Here, we present just a collection of beans (JACOB): an integrated batch‐based framework designed for the rapid development of computational chemistry applications. The framework expedites developer productivity by handling the generic infrastructure tier, and can be easily extended by user‐specific scientific code. Paradigms from enterprise software engineering were rigorously applied to create a scalable, testable, secure, and robust framework. A centralized web application is used to configure and control the operation of the framework. The application‐programming interface provides a set of generic tools for processing large‐scale noninteractive jobs (e.g., systematic studies), or for coordinating systems integration (e.g., complex workflows). The code for the JACOB framework is open sourced and is available at: www.wallerlab.org/jacob . © 2013 Wiley Periodicals, Inc.