Catalyst‐Free Enantiospecific Olefination with In Situ Generated Organocerium Species

Described is the in situ formation of triorganocerium reagents and their application in catalyst‐free Zweifel olefinations. These unique cerium species were generated through novel exchange reactions of organohalides with n‐Bu₃Ce reagents. The adequate electronegativity of cerium allowed for compensating the disadvantages of both usually functional‐group‐sensitive organolithium species and less reactive organomagnesium reagents. Exchange reactions were performed on aryl and alkenyl bromides, enabling enantiospecific transformations of chiral boron pinacol esters. Finally, these new organocerium species were engaged in selective 1,2‐additions onto enolisable and sterically hindered ketones.     

iso-PsE, a new pseudopterosin

We describe the discovery of a new member of the pseudopterosin class of marine natural products. Its structure is isomeric with that of pseudopterosin E and has therefore been given the name iso-PsE.     

Unusual sterically controlled regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine. Straightforward access to highly substituted nicotinic acid derivatives

[Structure: see text] Lithiation of 5-bromonicotinic acid protected as secondary or tertiary amide as well as (4,4'-dimethyl)oxazoline with lithium amides is reported. The unusual C-2 and C-4 regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine using LTMP versus LDA was observed, providing a new route to substituted nicotinic acid scaffolds. The methodology was applied to the synthesis of novel C-4 and C-6 arylated 5-bromonicotinic acids.     

Pd‐Catalyzed Decarboxylative Cross‐Coupling of 2‐Carboxyazine N‐Oxides with Various (Hetero)aryl Halides

Decarboxylative cross‐coupling reactions of substituted 2‐carboxyazine N‐oxides, with a variety of (hetero)aryl halides, by bimetallic Pd⁰/Cu^I and Pd⁰/Ag^I catalysis are reported. Two possible pathways, a conventional bimetallic‐catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C?H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2‐carboxyazine series.     

Assay Development and Identification of the First Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase Inhibitors

In the fight towards eradication of malaria, identifying compounds active against new drug targets constitutes a key approach. Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (PfHPPK) has been advanced as a promising target, as being part of the parasite essential folate biosynthesis pathway while having no orthologue in the human genome. However, no drug discovery efforts have been reported on this enzyme. In this study, we conducted a three-step screening of our in-house antifolate library against PfHPPK using a newly designed PfHPPK-GFP protein construct. Combining virtual screening, differential scanning fluorimetry and enzymatic assay, we identified 14 compounds active against PfHPPK. Compounds’ binding modes were investigated by molecular docking, suggesting competitive binding with the HMDP substrate. Cytotoxicity and in vitro ADME properties of hit compounds were also assessed, showing good metabolic stability and low toxicity. The most active compounds displayed low micromolar IC₅₀ against drug-resistant parasites. The reported hit compounds constitute a good starting point for inhibitor development against PfHPPK, as an alternative approach to tackle the malaria parasite.     

Modified perturbation-variation method for calculating spin-spin coupling constants

Fermi contact nuclear spin-spin coupling constants are calculated by a perturbation-variation method. The trial function used includes a singularity at the nucleus and a variational term. Application to the HD molecule was carried out with an LCAO MO wavefunction expanded over a minimal Slater basis set. Using reasonable values of atomic orbital exponents α the calculated values bracket the experimental value of J_HD.     

AN ANALYSIS OF PORPHYRIDIUM ABSORPTION BANDS WITH A DIGITAL SPECTROPHOTOMETER

Abstract— –Numerical absorbance values treated by a computer allow one to easily obtain precise absorption spectra from intact cells or extracts. An attempt has been made to determine the number and position of the individual bands by the difference spectra and the fourth derivative method. These two methods resulted in an accurate curve resolution with single Gaussian components and yielded relative proportions of chl a forms in Porphyridium.     

ELECTROPHORETIC AND SPECTROPHOTOMETRIC STUDIES OF CHLOROPHYLL-PROTEIN COMPLEXES FROM TOBACCO CHLOROPLASTS. ISOLATION OF A LIGHT HARVESTING PIGMENT PROTEIN COMPLEX WITH A MOLECULAR WEIGHT OF 70,000

Abstract— …After a short-term solubilization with sodium dodecyl sulphate, chloroplast membranes of tobacco were separated by polyacrylamide gel electrophoresis into three chlorophyll-protein complexes. In addition to the two major complexes termed I and II_c corresponding respectively to P700 chlorophyll a -protein and light-harvesting chlorophyll a/b -protein described by Thornber (1975), a relatively stable complex termed II_a has been observed. This new complex has an apparent molecular weight of 70,000 daltons and possesses Chl a and b.
Complexes I, II_a and II_C have been isolated and precise spectroscopic analyses have been performed. Fourth derivative analyses of low temperature absorption spectra suggest that complex II_a seems more representative than II_C of chlorophyll a forms present in intact thylakoid membranes.
Moreover, the electrophoretic study reveals that CP_I and CP_II are composed of only one polypeptidic subunit with respective molecular weights of 68,000 and 24,000 daltons.     

Deprotonation of benzoxazole and oxazole using lithium magnesates

The first deprotonations of oxazole and benzoxazole using lithium magnesates are described. The reactions occurred in tetrahydrofuran at room temperature using 1/3 equiv of lithium tributylmagnesate. As 2-lithiooxazole and 2-lithiobenzoxazole, lithium tri(2-oxazolyl)magnesate and lithium tri(2-benzoxazolyl)magnesate very rapidly and completely isomerized to the more stable 2-(isocyano)enolate and 2-(isocyano)phenolate type structures, respectively, a result shown by NMR analysis. The isolation of 2-substituted oxazoles and benzoxazoles in medium to good yields after electrophilic trapping was interpreted in two ways: (1) the equilibration between the open and closed structures is faster than the trapping of the open isomers, and the closed isomers are more reactive than the open ones, or (2) the open isomers react with electrophiles in a intramolecular Passerini type reaction. The nonreactivity of the 2-(isocyano)enolate type structure toward anisaldehyde in the absence of lithium bromide makes the intramolecular Passerini type reaction more plausible.     

Diastereoselective dearomatization of resorcinols directed by a lactic acid tether: unprecedented enantioselective access to p-quinols

An operationally simple oxidative dearomatization of resorcinol derivatives is reported that employs an inexpensive chiral directing group. The method provides access to a variety of p-quinol derivatives in good yield and diastereoselectivity. A short reductive process affords 4-hydroxy-4-alkylcyclohexenone derivatives in excellent yields and enantiomeric excesses.