Synthesis and Anticoagulant Activity of Bioisosteric Sulfonic‐Acid Analogues of the Antithrombin‐Binding Pentasaccharide Domain of Heparin

Two pentasaccharide sulfonic acids that were related to the antithrombin‐binding domain of heparin were prepared, in which two or three primary sulfate esters were replaced by sodium‐sulfonatomethyl moieties. The sulfonic‐acid groups were formed on a monosaccharide level and the obtained carbohydrate sulfonic‐acid esters were found to be excellent donors and acceptors in the glycosylation reactions. Throughout the synthesis, the hydroxy groups to be methylated were masked in the form of acetates and the hydroxy groups to be sulfated were masked with benzyl groups. The disulfonic‐acid analogue was prepared in a [2+3] block synthesis by using a trisaccharide disulfonic acid as an acceptor and a glucuronide disaccharide as a donor. For the synthesis of the pentasaccharide trisulfonic acid, a more‐efficient approach, which involved elongation of the trisaccharide acceptor with a non‐oxidized precursor of the glucuronic acid followed by post‐glycosidation oxidation at the tetrasaccharide level and a subsequent [1+4] coupling reaction, was elaborated. In vitro evaluation of the anticoagulant activity of these new sulfonic‐acid derivatives revealed that the disulfonate analogue inhibited the blood‐coagulation‐proteinase factor Xa with outstanding efficacy; however, the introduction of the third sulfonic‐acid moiety resulted in a notable decrease in the anti‐Xa activity. The difference in the biological activity of the disulfonic‐ and trisulfonic‐acid counterparts could be explained by the different conformation of their L ‐iduronic‐acid residues.     

TEM studies of structure in OFHC copper processed by equal channel angular rolling

In this study, UFG (ultrafine-grained) structure formed through ECAR (equal-channel angular rolling) process has been studied by methods of electron microscopy. The microstructure, mechanical properties and microhardness were investigated in OFHC (oxygen free high conductivity) copper after 1st–13th passes. The interpretation of microstructure changes was performed using a model which describes mechanism of UFG structures formation. It was found that ECAR is a tool used for the purpose of achieving significant structural refinement resulting in a final grain size d ～ 400 nm. Moreover, this method provides such specific structural changes which have highly advantageous influence on mechanical properties (yield stress, ultimate tensile strength, reduction of area) as well as microhardness.     

Chemoenzymatic synthesis of both enantiomers of 3-hydroxy- and 3-amino-3-phenylpropanoic acid

Ethyl (S)-3-hydroxy-3-phenylpropionate (S)-2 was obtained by the asymmetric reduction of ethyl 3-phenyl-3-oxopropionate 1 with the yeast Saccharomyces cerevisiae (ATCC 9080). The kinetic resolution of racemic ethyl 2-acetoxy-3-phenyl-propionate rac-3 with the same microorganism, gave after hydrolysis ethyl (R)- and (S)-3-hydroxy-3-phenylpropionates (R)-2 and (S)-2 which were converted by a straightforward series of reactions to the enantiomers of 3-amino-3-phenyl-propionic acids (S)-6 and (R)-6. The asymmetric reduction and hydrolytic kinetic resolution were also tested with several other whole cell systems under a variety of conditions.     

Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Several cinchona based squaramide catalysts were applied to the asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yields and enantioselectivities. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.     

Synthesis of the non-reducing end trisaccharide of the antithrombin-binding domain of heparin and its bioisosteric sulfonic acid analogues

A glucoronic acid-containing trisaccharide related to the antithrombin-binding DEFGH domain of heparin and its methanesulfonic acid analogues were synthesized. Trisaccharides without sulfonic acid content or possessing a sulfonatomethyl moiety at position 2 or 6 of unit F were prepared in high yields by [DE+F] couplings using the same disaccharide uronate donor, respectively. Synthesis of the trisaccharide with a 3-deoxy-3-sulfonatomethyl function was accomplished in three different pathways, from which a [D+EF] coupling and applying a non-oxidized precursor of the glucuronic acid afforded the trisaccharide in the highest yield.     

Conformal Covariance and Positivity of Energy in Charged Sectors

It has been recently noted that diffeomorphism covariance of a Chiral Conformal QFT in the vacuum sector automatically ensures Möbius covariance in all charged sectors. In this article it is shown that diffeomorphism covariance and positivity of the energy in the vacuum sector even ensure the positivity of energy in the charged sectors.The main observation of this paper is that the positivity of energy — at least in case of a Chiral Conformal QFT — is a local concept: it is related to the fact that the energy density, when smeared with some local nonnegative test functions, remains bounded from below (with the bound depending on the test function).The presented proof relies in an essential way on recently developed methods concerning the smearing of the stress-energy tensor with nonsmooth functions.     

COS and C3S2: The discovery and chemistry of two important inorganic sulfur compounds

Although CO and CO₂ have been known since the dawn of chemistry and although CS₂ was discovered as early as 1796,¹ COS and C₃S₂ were not discovered until 1867 and 1893, respectively. This article considers the circumstances surrounding their discoveries as well as later reports on their chemistries. Both compounds were first prepared by Hungarian chemists, and both are of great theoretical and practical importance. The discovery and preparation of COS by Károly (Karl) Than is a beautiful example of logical chemical thinking, whereas the serendipitous discovery of C₃S₂ by Béla Lengyel is a case study in careful experimentation and keen observation. The sesquicentennial anniversary of the birth of Than, who is regarded as the founder of modern Hungarian chemistry, makes this article of timely significance. Since both he and his student Lengyel and their accomplishments have been neglected by English-speaking chemists and historians of chemistry, they are briefly discussed in this article.