Albert Eschenmoser

Mineral induced formation of sugar phosphates

Glycolaldehyde phosphate, sorbed from highly dilute, weakly alkaline solution into the interlayer of common expanding sheet structure metal hydroxide minerals, condenses extensively to racemic aldotetrose-2,4-diphosphates and aldohexose-2,4,6-triphosphates. The reaction proceeds mainly through racemic erythrose-2,4-phosphate, and terminates with a large fraction of racemic altrose-2,4,6-phosphate. In the absence of an inductive mineral phase, no detectable homogeneous reaction takes place in the concentration- and pH range used. The reactant glycolaldehyde phosphate is practically completely sorbed within an hour from solutions with concentrations as low as 50 µm; the half-time for conversion to hexose phosphates is of the order of two days at room temperature and pH 9.5. Total production of sugar phosphates in the mineral interlayer is largely independent of the glycolaldehyde phosphate concentration in the external solution, but is determined by the total amount of GAP offered for sorption up to the capacity of the mineral. In the presence of equimolar amounts of rac-glyceraldehyde-2-phosphate, but under otherwise similar conditions, aldopentose-2,4,-diphosphates also form, but only as a small fraction of the hexose-2,4,6-phosphates.

Evidence for the production of trioxygen species during antibody-catalyzed chemical modification of antigens

Recent work in our laboratory showed that products formed by the antibody-catalyzed water-oxidation pathway can kill bacteria. Dihydrogen peroxide, the end product of this pathway, was found to be necessary, but not sufficient, for the observed efficiency of bacterial killing. The search for further bactericidal agents that might be formed along the pathway led to the recognition of an oxidant that, in its interaction with chemical probes, showed the chemical signature of ozone. Here we report that the antibody-catalyzed water-oxidation process is capable of regioselectively converting antibody-bound benzoic acid into para-hydroxy benzoic acid as well as regioselectively hydroxylating the 4-position of the phenyl ring of a single tryptophan residue located in the antibody molecule. We view the occurrence of these highly selective chemical reactions as evidence for the formation of a short-lived hydroxylating radical species within the antibody molecule. In line with our previously presented hypothesis according to which the singlet-oxygen (1O*2) induced antibody-catalyzed water-oxidation pathways proceeds via the formation of dihydrogen trioxide (H2O3), we now consider the possibility that the hydroxylating species might be the hydrotrioxy radical HO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{_{3}}^{{\bullet}}}}\end{equation*}\end{document}, and we point to the remarkable potential of this either H2O3- or O3-derivable species to act as a masked hydroxyl radical (HO•) in a biological environment.

Strain release in C-H bond activation?

What a relief! In 1955 the principle of strain release was put forward to explain the differing reactivity of axial and equitorial alcohols during oxidation. Our findings suggest that this same rationale may account for the differing rates of activation between axial and equitorial C–H bonds in C–H activation processes. In conjunction with steric and electronic considerations, strain-release can be used to qualitatively predict relative rates and site specificity of C–H activation in complex settings.

Formation of glycolaldehyde phosphate from glycolaldehyde in aqueous solution

Amidotriphosphate (0.1 M) in aqueous solution at near neutral pH in the presence of magnesium ions (0.25 M) converts glycolaldehyde (0.025 M) within days at room temperature into glycolaldehyde phosphate in (analytically) nearly quantitative yields (76% in isolated product). This robust phosphorylation process was observed to proceed at concentrations as low as 30 μM glycolaldehyde and 60 μM phosphorylation reagent under otherwise identical conditions. In sharp contrast, attempts to achieve a phosphorylation of glycolaldehyde with cyclotriphosphate (‘trimetaphosphate’) as phosphorylating reagent were unsuccessful. Mechanistically, the phosphorylation of glycolaldehyde with amidotriphosphate is an example of intramolecular delivery of the phosphate group.

Enhanced reactivity in dioxirane C-H oxidations via strain release: a computational and experimental study.

The site selectivities and stereoselectivities of C-H oxidations of substituted cyclohexanes and trans-decalins by dimethyldioxirane (DMDO) were investigated computationally with quantum mechanical density functional theory (DFT). The multiconfiguration CASPT2 method was employed on model systems to establish the preferred mechanism and transition state geometry. The reaction pathway involving a rebound step is established to account for the retention of stereochemistry. The oxidation of sclareolide with dioxirane reagents is reported, including the oxidation by the in situ generated tBu-TFDO, a new dioxirane that better discriminates between C-H bonds on the basis of steric effects. The release of 1,3-diaxial strain in the transition state contributes to the site selectivity and enhanced equatorial C-H bond reactivity for tertiary C-H bonds, a result of the lowering of distortion energy. In addition to this strain release factor, steric and inductive effects contribute to the rates of C-H oxidation by dioxiranes.

New Insights into the Mechanism and an Expanded Scope of the Fe(III)-Mediated Vinblastine Coupling Reaction

A definition of the scope of aromatic substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examination of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addition to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aqueous buffer may be radical mediated, the studies provide new opportunities for the preparation of previously inaccessible vinblastine analogs and define powerful new methodology for the synthesis of indole-containing natural and unnatural products.

Towards a Chemical Etiology of Nucleic Acid Structure

To Leslie E. Orgel, arbiter elegantiarum of contemporary origin-of-life science and far-sighted pioneer of non-enzymic molecular replication, on the occasion of his 70th birthday, with cordial congratulations and best wishes.In the sequel of some general remarks on a chemical etiology of nucleic-acid structure, the paper presents a reproduction of the sequence of slides which were shown in the authors lecture ‘Pyranosyl-RNA’ at the 8. ISSOL Conference in Orléans. Each slide figure is accompanied by a short explanatory comment.

Notiz über einen Zugang zu β, γ‐ungesättigten Carbonsäurederivaten mit Hilfe der Amidacetal‐Claisenumlagerung. Über synthetische methoden, 17. Mitteilung

Note on a preparation of β, γ-unsaturated carboxylic acid derivatives using the amide acetalClaisenrearrangement 3-(Trimethylsilyl)allyl alcohols smoothly undergo the amide acetal Claisen rearrangement furnishing allyl silanes. Subsequent protolysis with HF at −20° provides a convenient, stereoselective method for the preparation of β, γ-unsaturated carboxylic acid derivatives. Three model examples illustrate the procedure.

Ozone in biology

In this issue of PNAS, Babior et al. (1) extend the published series of experiments by Wentworth et al. (2–5) in which it was shown that antibodies catalyze the generation of ozone by a water oxidation pathway. The overall process is postulated to involve more than one equivalent of the lower-energy singlet state of molecular oxygen (1O2) and to proceed via dihydrogen trioxide (H2O3) as a key intermediate (Eq. 1). Alternatively, the involvement of a higher-energy singlet state of oxygen may be considered The presumed role of the antibody molecule is to organize the short-lived reactant 1O2 (t1/2 1O2 in water is ≈1 μs) and water into a productive complex and also stabilize the H2O3 intermediate [t1/2 H2O3 at room temperature in water is ≈20 ms; t1/2 H2O3 at room temperature in anhydrous acetone is ≈ 3 min (P. Wentworth, Jr., personal communication). Because all antibodies, regardless of source, species, or antigenic specificity, can catalyze this reaction (2), it is most properly thought of as a newly discovered effector function of antibodies. Some of the early questions about this reaction concerned the source of the 1O2 as well as its biological significance. These questions were approached in a recent study by Wentworth et al. (4) in which they demonstrated that activated white cells, which have been shown to produce 1O2 (6), could serve as a substrate source for the antibody-catalyzed reaction. In this instance, the catalysts are presumed to be the Ig molecules bound to the neutrophil plasma membrane via the FcγIII receptors. As will be discussed below, this arrangement of reactants and catalysts may comprise a highly efficient killing system. …

Synthetic corrin complexes

In 1963 a description of the work in progress at the laboratories of the E.T.H. towards the synthesis of corrins was presented (Eschenmoser 1963). At that time, we were able to report the synthesis of the analytically and spectroscopically well defined crystalline nickel complex I; however, the ultimate problem of these studies, namely the cyclization of such precorrinoid systems to corrin complexes, remained unsolved. Since then, this final goal has been attained; nickel (n) as well as cobalt (III) complexes of the pentamethylcorrin ligand II (R = CN, H) have been prepared, thus bringing the corrin system within the reach of synthetic organic chemistry.