A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones

Enzymatic core components from trans‐acyltransferase polyketide synthases (trans‐AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans‐AT PKS pathways, including those for pederin, oocydins, and toblerols. Using the oocydin pathway homologue (OocK) from Serratia plymuthica 4Rx13 and N‐acetylcysteamine (SNAC) thioesters as test surrogates for acyl carrier protein (ACP)‐tethered intermediates, we show that the enzyme inserts oxygen into β‐ketoacyl moieties to yield malonyl ester SNAC products. Based on these data and the identification of a non‐hydrolyzed oocydin congener with retained ester moiety, we propose a unified biosynthetic pathway of oocydins, haterumalides, and biselides. By providing access to internal ester, carboxylate pseudostarter, and terminal hydroxyl functions, oxygen insertion into polyketide backbones greatly expands the biosynthetic scope of PKSs.     

NMR‐Structural Investigations of a β3‐Dodecapeptide with Proteinogenic Side Chains in Methanol and in Aqueous Solutions

The structural properties of an all‐β³‐dodecapeptide with the sequence H‐β‐HLys(N^ε‐CO(CH₂)₃‐S Acm)‐β‐HPhe‐β‐HTyr‐β‐HLeu‐β‐HLys‐β‐HSer‐β‐HLys‐β‐HPhe‐β‐HSer‐β‐HVal‐β‐HLys‐β‐HAla‐OH ( 1 ) have been studied by two‐dimensional homonuclear ¹H‐NMR and by CD spectroscopy. In MeOH solution, high‐resolution NMR spectroscopy showed that the β‐dodecapeptide forms an (M)‐3₁₄‐helix, and the CD spectrum corresponds to the pattern expected for an (M)‐3₁₄‐helical secondary structure. In aqueous solution, however, the peptide adopts a predominantly extended conformation without regular secondary‐structure elements, which is in agreement with the absence of the characteristic trough near 215 nm in the CD spectrum. The NMR and CD measurements with solutions of 1 in MeOH containing 3M urea further indicated that the peptide retains the regular secondary structural elements under these conditions, whereas, after addition of 40% (v/v) H₂O to the MeOH solution, the large ¹H‐chemical‐shift dispersion indicative of a defined spatial peptide fold was lost. The β³‐dodecapeptide is – so far – the longest β‐peptide shown to adopt a regular (M)‐3₁₄‐helix conformation in an organic solvent. The observation that the structure of this long β³‐peptide is not maintained in aqueous solution indicates that the (M)‐3₁₄‐fold is primarily stabilized by short‐range interactions.     

Asymmetric base-mediated epoxide isomerisation

The base-mediated rearrangement of epoxides into allylic alcohols is a well-known synthetic transformation. The first enantioselective version of the reaction using a chiral base was reported in 1980. Since then, the reaction has received a lot of attention mostly due to the great usefulness of chiral allylic alcohols in organic synthesis. Major breakthroughs in the area were the first report on using a sub-stoichiometric amount of chiral base, and the development of chiral bases for a true catalytic reaction protocol. The present review covers the time from when the first asymmetric epoxide isomerisation reaction was reported (1980) up to now, focusing on the period 1997-2001.     

Fabrication of Sensitive Potentiometric Cholesterol Biosensor Based on Co3O4 Interconnected Nanowires

Highly sensitive, selective, reliable and inexpensive cholesterol biosensors are highly demanded for the routine monitoring of cholesterol molecules in order to prevent heart failure incidents. In this study, Co₃O₄ nanostructures are synthesized using polyvinyl pyrrolidone surfactant as growth template by a low temperature aqueous chemical growth method. The morphology of nanostructures was investigated by scanning electron microscopy and X‐ray diffraction techniques. The nanostructures exhibit interconnected nanowires like morphology with interconnected network of nanowires. The nanostructures of Co₃O₄ are polycrystalline. The cholesterol oxidase was physically adsorbed on the interconnected nanowires of Co₃O₄ for the chemical sensing of cholesterol molecules. The sensor device detected a wide range of cholesterol from 1×10^?7 M to 1×10^?3 M concentrations with sensitivity of ?94.031 mV/decade. A detection limit of 0.035×10^?7 M cholesterol concentration was observed and a fast response time of 10 s was also noticed. The fabricated device is highly stable, selective, sensitive, reproducible and repeatable. All the collected information about presented cholesterol biosensor indicates its potential application for the monitoring of cholesterol concentrations from human blood serum and real‐life samples.     

A general,recursive, and open‐ended response code

We present a new implementation of a recent open‐ended response theory formulation for time‐ and perturbation‐dependent basis sets (Thorvaldsen et al., J. Chem. Phys. 2008, 129, 214108) at the Hartree–Fock and density functional levels of theory. A novel feature of the new implementation is the use of recursive programming techniques, making it possible to write highly compact code for the analytic calculation of any response property at any valid choice of rule for the order of perturbation at which to include perturbed density matrices. The formalism is expressed in terms of the density matrix in the atomic orbital basis, allowing the recursive scheme presented here to be used in linear‐scaling formulations of response theory as well as with two‐ and four‐component relativistic wave functions. To demonstrate the new code, we present calculations of the third geometrical derivatives of the frequency‐dependent second hyperpolarizability for HSOH at the Hartree–Fock level of theory, a seventh‐order energy derivative involving basis sets that are both time and perturbation dependent. © 2014 Wiley Periodicals, Inc.     

(E,E,E)‐1,3,5‐Tris[4‐(acetyl­sulfan­yl)­styr­yl]­benzene toluene hemisolvate

The first crystal structure of a three‐terminal sulfur end‐capped oligo­phenyl­ene­vinyl­ene, C₃₆H₃₀O₃S₃·0.5C₇H₈, has been determined at 122 (1) K. The mol­ecular threefold symmetry is not utilized in the crystal structure. It is confirmed that the double bonds have been fully transformed into a trans configuration by iodine treatment.     

One-pot three-component reaction for the synthesis of alpha-(aminoethyl)-alpha,beta-enones

[reaction: see text] The synthesis of alpha-substituted alpha,beta-enones by a new metal iodide-promoted one-pot three-component reaction involving commercially available cyclopropyl ketones, aldehydes, and secondary amines followed by base treatment is described.     

Hyperpolarization of 13C through order transfer from parahydrogen: a new contrast agent for MRI

The order within proton pairs in organic molecules, resulting from hydrogenation with parahydrogen, can be transferred in great part to nearby carbon 13 spins through adequate field manipulations. The molecules with hyperpolarized 13C thus obtained can be used as new contrast agents of high efficiency in MRI. After a brief presentation of the hydrogenation process and apparatus, in relatively low magnetic field, we describe the procedure of order transfer to the 13C spins through a sudden drop from the initial field to zero field followed by an adiabatic remagnetization. The expected final polarizations in the absence of relaxation are given for several compounds. Finally, we show an example of MR images observed in vivo on animals as an illustration of the contrast capacity of this new method.     

A novel oxidative rearrangement of 6-methoxypyran-2-ones

As part of our continuing studies of pyrone-containing natural products, a series 6-methoxypyran-2-ones were synthesized. These were found to react with molecular oxygen at 20 degrees C, and this novel reaction yielded a series of highly functionalized alpha,beta-butenolides. [reaction: see text]