Synthesis of cephalosporins carrying isoxazolyl acetamido and related side chains

Starting from 3,5-dimethylisoxazole the carboxylic acids I and V, the amino acids VIII (L-) and IX (D-), and the ureido acids X (L-) and XI (D-) were prepared, which were used for the synthesis of the new cephalosporins XVIIb, XXa-c (L-), and XXIb (D-). Thein vitro antibacterial activity of these semi-synthetic antibiotics was studied. The resorption of XVIIb was investigated in mice.Research Group for Antibiotics of the Hungarian Academy of Sciences, H-4010 Debrecen, P.O. Box 70, Hungary. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1524–1535, November, 1998.     

A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination

Mets motifs, which refer to methionine-rich sequences found in the high-affinity copper transporter Ctr1, also appear in other proteins involved in copper trafficking and homeostasis, including other Ctrs as well as Pco and Cop proteins isolated from copper-resistant bacteria. To understand the coordination chemistry utilized by these proteins, we studied the copper binding properties of a peptide labeled Mets7-PcoC with the sequence Met-Thr-Gly-Met-Lys-Gly-Met-Ser. By comparing this sequence to a series of mutants containing noncoordinating norleucine in place of methionine, we confirm that all three methionine residues are involved in a thioether-only binding site that is selective for Cu(I). Two independent methods, one based on mass spectrometry and one based on rate differences for the copper-catalyzed oxidation of ascorbic acid, provide an effective K(D) of approximately 2.5 microM at pH 4.5 for the 1:1 complex of Mets7-PcoC with Cu(I). These results establish that a relatively simple peptide containing an MX(2)MX(2)M motif is sufficient to bind Cu(I) with an affinity that corresponds well with its proposed biological function of extracellular copper acquisition.     

Stereoselective synthesis of functionalised triol units by SnCl4 promoted allylation of α-benzyloxyaldehydes: crucial role of the stoichiometry of the Lewis acid

Enantiomerically pure syn-anti and syn-syn configured triol units are efficiently synthesized by the SnCl₄ mediated allylation of chiral α-benzyloxyaldehydes with the uniquely functionalised allylstannane 9. Remarkably, the stereochemistry of the adducts is solely governed by the amount of Lewis acid employed.     

Phosphonio‐benzophospholide Zwitterions as Bridging 8e‐Donor Ligands: Synthetic and Mechanistic Studies

Reactions of the phosphonio‐benzophospholide π‐complexes 3a, b[Cr] with [M(CO)₅(olefin)] or of the σ‐complexes 2a, b[M] (M = Cr, Mo, W) with [M(CO)₃(aren)] lead to the first binuclear complexes 4a, b[CrM] featuring phosphonoio‐benzophospholides as μ‐bridging 8e‐donor ligands to two group 6 metal atoms. The constitution of the products was determined by spectroscopic and X‐ray diffraction studies. Mixed complexes with both group 6 and 7 metals were not accessible. Mechanistic studies showed that the reactions follow a complicated mechanism whose single steps may involve transfer of either M(CO)_n fragments or single CO ligands between complexes; the latter are associated with a σ/π‐coordination isomerization of the benzophospholide unit. Competition between both reaction channels can lead to the formation of product mixtures whose composition is controlled by the relative thermodynamic stabilities of the products. Computational studies suggest that in the more stable isomer of heterobimetallic complexes 4a, b[MM′] end‐on coordination to the heavier and side‐on coordination to the lighter metal atom is preferred.     

Synthesis and Electron-Diffraction Structure of all-cis-[5.5.5.5]Fenestrane

The efficient synthesis of all-cis-[5.5.5.5]fenestrane ( 2 ) from the readily available intermediate 3 allowed the electron-diffraction analysis of 2 . This structure analysis revealed long C? C bonds in the central C(C)₄ fragment and a twist-envelope conformation for the four cyclopentane substructures. The four bridgehead H-atoms are in a synclinal rather than an ecliptic position with an approximate D₂ symmetry of 2 . Planarizing distortions are evident from the opposite bond angles at the central C-atom being 116.2 ± 0.5° with the remaining four being 103.7 ± 0.2°.     

Carl Djerassi,structural chemist turned author/playwright,has published a new autobiography,In Retrospect: From the Pill to the Pen

The stereochemist and steroid chemist Carl Djerassi turned poet, novelist, and playwright, published another autobiography taking stock of his prolific production of science-in-fiction during the last decades. He has been successful in bridging the gap between science and art.     

E. Thomas Strom and Vera V. Mainz (eds): The posthumous Nobel Prize in chemistry. Volume 1. Correcting the errors and oversights of the Nobel Prize committee

Structural Chemistry -     

A Multicolumn Ion Chromatographic Determination of Nitrate and Sulfate in Waters Containing Humic Substances

Abstract

A three-column ion chromatographic system for the removal of humic substances from natural waters, and subsequent on-line concentration and determination of nitrate and sulfate using non-suppressed ion chromatography is presented. Humic substances are removed using disposable adsorption columns packed with chemically bonded amine silica material. The sample is directly transfered to an ion exchange column where the anions are concentrated ca 10 times. After reversing the flow, the ions are transferred to a third column where they are separated and quantified. The detection limit is less than 1 mg L^?1 of nitrate or sulfate in water containing 45mgL^?1 of humic acid.     

Synthesis and Structural Assignment of 1-O-Acetyl-2,3,5-tri-O-benzoyl-4-(thymin-1-yl)-α-l-lyxofuranose

Abstract

Analogues of nucleosides in which the nucleobase is fixed onto the C-4 of the sugar moiety are generally prepared either from 4,5-unsaturated sugar derivatives or via a formaldehyde condensation.¹ We tested the furanosyl bromide reactivity of 1 ² towards a series of nucleophiles, mostly azides or cyanides, without success. Conversely, the nucleosidation of 1 using 5-methyl-2,4-bis(trimethyl-silyloxy)pyrimidine in the presence of stannic chloride took place at the second anomeric position (C-4) and led to the isolation in acceptable yield (47%) of a unique anomer 2 (Scheme 1).