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We present alkali salts of amino acids as functional, non-toxic, non-hazardous, non-volatile, chemically stable, and cheap alkaline additives for common acidic corrosion inhibitors. The resulting mixtures have been evaluated for Co, Ni, and Cu leaching and were analyzed by chip filter assay, potentiodynamic polarization measurements, electrochemical impedance measurements, and gravimetry for corrosion protection of iron and steel in aqueous environment at slightly alkaline pH. Leaching of Co and Ni was found to depend on the corresponding complex stabilities. Taurine (Tau) as well as aminohexanoic acid (AHX) leads to low leaching of Co and Ni. Particularly AHX is an attractive low leaching additive leading to lower Co and Ni concentrations in solution than currently used amino alcohols. Glu and Tau were found to synergistically interact with several acidic corrosion inhibitors of the carboxylic acid and the phosphonic acid type. Tau had a particularly positive impact on the protective properties of carboxyphosphonic acids. Glu had also a positive effect on the anti-corrosive properties of several acidic corrosion inhibitors and served as an anti-scalant. Alkali salts of Glu and Tau might thus serve as commercially and ecologically attractive substitutes for current alkaline additives to acidic corrosion inhibitors.

Herein, the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31 is described. Although the flexible Tris‐based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a rigid adamantane core dominated flexible tripodal compounds with micromolar binding and hemagglutination inhibition constants. Simulation studies indicated increased conformational penalties for long OEG spacers. Using a systematic approach with molecular modeling and simulations as well as biophysical analysis, these findings emphasize on the importance of the scaffold rigidity and the challenges associated with the spacer length optimization.

The edible fungus Pleurotus sapidus (PSA) is a particularly interesting biocatalytic system for allylic oxidation and has a remarkably broad substrate range from terpenoids to fatty acids. The oxidations are most likely catalyzed by a lipoxygenase and involve the formation of peroxides via radical intermediates in the first rate-limiting step. We provide herein a rationalization of the observed regioselectivity of these conversions by means of computational determination of bond dissociation enthalpies of a set of tailor-made spirocyclic terpenoids. It was found that only strongly activated allylic positions (BDH298 of

Chiral spirocyclic terpenoids are abundant natural flavors with significant impact particularly on the food industry. Chromatographic methods for analytical and preparative separation of these compounds are therefore of high interest to natural product chemists in academia and industry. Gas chromatography on chiral stationary phases is currently the standard method for the separation of volatile terpenoids, limiting the scale to analytical quantities. We report herein high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) protocols for the chiral separation of several racemic spirocyclic terpenoids such as the important flavors theaspirane and vitispirane. A screening of mobile phases and 16 commercially available chiral stationary phases (CSPs) largely based on polysaccharides led to identification of protocols for the separation of all terpenoids tested. SFC methods were found to be particularly useful for the separation of these spirocyclic flavors due to the volatility and low polarity of the compounds. The reported chiral HPLC and SFC protocols are scalable alternatives to gas chromatographic separations of volatile terpenoid flavors.

We have recently described the synthesis of diazabicyclo[4.X.0]alkanes and their use as ligands for the prostate specific membrane antigene (PSMA). The key step of our synthetic route toward these diazabicycloalkanes is an oxidative cleavage of a bicyclic diol moiety followed by the attack of a nitrogen nucleophile to the resulting intermediate bisaldehyde. We herein describe the mechanism of this ring closure and its stereochemical consequences. In addition, we report a convenient method for trapping intermediate bisaldehydes by Wittig reagents. This trapping allows the synthesis of 3,5-disubstituted proline derivatives, which are shown to be versatile precursors for functionalized diazabicycloalkane dipeptide mimetics.

A new synthetic route to enantiomerically pure disubstituted derivatives of cyclic amino acids is reported. Key step of this synthesis is an oxidative cleavage of azabicycloalkene precursors that are synthesized in enantiomerically pure form via aza-Diels–Alder reaction. A range of different disubstituted pipecolic acid derivatives has been synthesized and their structure has been evaluated by X-ray analysis.

Carbohydrates are involved in a wide range of biological processes of pharmaceutical relevance. The selective recognition of carbohydrates is therefore of great interest in biology and medicine. In this study we present the synthesis of fluorescent multimeric benzoboroxoles and the analysis of multivalent binding processes to immobilized carbohydrate arrays by fluorescence spectroscopy. We observed high binding affinities of trimeric benzoboroxoles by determination of KDsurf values for their interaction with α-Gal on glass chips. The observed KDsurf values were in the mid-nM range (49 and 104 nM) and are comparable to the KDsurf values for binding of natural lectins, such as that of ConA to immobilized α-Man (79 nM). The array technology was found to be an excellent tool for studying the binding processes of multivalent lectin mimetics with respect to profiling and quantitation.

Herein, we report the synthesis of two enantiomeric DOTAZA esters and a related DOT3AZA ester. These compounds are tunable analogues of the well-known chelator DOTA and can be easily functionalized through click chemistry of the side-chain azide groups. Like DOTA, DOTAZA forms complexes with various di- and trivalent metals, as demonstrated in the synthesis and structural analysis of CuDOTAZA and the preparation of GdDOTAZA.

Scope Celiac disease is an autoimmune disorder caused by failure of oral tolerance against gluten in genetically predisposed individuals. The epithelial translocation of gluten-derived gliadin peptides is an important pathogenetic step; the underlying mechanisms, however, are poorly understood. Thus, we investigated the degradation and epithelial translocation of two different gliadin peptides, the toxic P31–43 and the immunogenic P56–68. As the size, and hence, the molecular weight of peptides might have an effect on the transport efficiency we chose two peptides of the same, rather short chain length. Methods and Results Fluorescence labeled P31–43 and P56–68 were synthesized and studied in a transwell system with human enterocytes. Fluorometric measurements were done to reveal antigen translocation and flow cytometry as well as confocal microscopy were used to investigate cellular uptake of peptides. Structural changes of these peptides were analysed by MALDI-TOF-MS. According to fluorescence intensities, significantly more P31–43 compared to P56–68 was transported through the enterocyte layer after 24 h incubation. In contrast to previous reports, however, mass spectrometric data do not only show a time-dependent cleavage of the immunogenic P56–68, but we observed for the first time the degradation of the toxic peptide P31–43 at the apical side of epithelial cells. Conclusion Considering the degradation of gliadin peptides by enterocytes, measurement of fluorescence signals do not completely represent translocated intact gliadin peptides. From our experiments it is obvious that even short peptides can be digested prior to the translocation across the epithelial barrier. Thus, the chain length and the sensibility to degradations of gliadin peptides as well as the integrity of the epithelial barrier seem to be critical for the uptake of gliadin peptides and the subsequent inflammatory immune response.

A family of efficient helix-initiating N-terminal caps X-Hel is introduced that expand the scope and versatility of the previously reported reporting conformational template Ac-Hel, (Kemp, D. S.; Allen, T. J.; Oslick, S. J. Am. Chem. Soc. 1995, 117, 6641-6657) and a working principle for predicting cap performance is described, based on structurally specific intramolecular hydrogen bond formation. Replacement of the N-acetyl by urethane, urea, or sulfonamide generated less efficient polypeptide helix inducers. The N-formyl cap is found to be equivalent to the N-acetyl and may provide more convenient quantitative helix reporting properties. Anionic N-caps derived from the series X = (-)O(2)C-(CH(2))(n)-CO, 0or = nor = 3, are superior to N-acetyl, as are N-acylglycyl and N-acyl-beta-aspartyl. The latter pair of caps permit introduction of the X-Hel functionality within a polypeptide chain, allowing control of helicity of a peptide sub-sequence. Applications of these capping functions are discussed. This work has been focused primarily on immediate practical goals directed toward enhancing the maximum helicity of isolated short to medium-sized peptides in aqueous solution, but its developing concepts and working hypotheses are likely to significantly enhance our understanding at a chemical level of the protein folding problem.

The first synthesis of an enantiomerically and diastereomerically pure 3-thiazoline via modified Asinger reaction using a galactose derived chiral auxiliary is described. The absolute configuration of this heterocyclic imine has been elucidated via X-ray analysis. In addition, the 3-thiazoline has been successfully derivatized under Ugi conditions.

The first highly diastereoselective (dr up to >95:5) hydrophosphonylation of heterocyclic imines by a chiral phosphorus nucleophile is introduced. Addition of binaphthol ester of phosphorus acid towards BF3-activated 3-thiazolines gives the corresponding (aR*,4R*)-4-thiazolidinylphosphonates almost exclusively as elucidated by X-ray analysis. # 2000 Elsevier Science Ltd. All rights reserved.

This paper describes a multicomponent approach to novel totally protected precursors of PNA-monomers via Ugi 4CC. The obtained bisamides are converted into several partially protected PNA-monomers or derivatives thereof using three different procedures. Methods for hydrolysis are shown to be dependent on the nature of the isocyano component required for Ugi 4CC. Several novel monomers suitable for oligomer synthesis are prepared demonstrating the high versatility of the reaction sequence.

Gram-negative bacteria often use N-acyl-honnoserine lactones (AHLs) as signal molecules to monitor their local population densities and to regulate gene-expression in a process called "Quorum Sensing" (QS). This cell-to-cell communication allows bacteria to adapt to environmental changes and to behave as multicellular communities. QS plays a key role in both bacterial virulence towards the host and symbiotic interactions with other organisms. Plants also perceive AHLs and respond to them with changes in gene expression or modifications in development. Herein, we report the synthesis of new AHL-derivatives for the investigation and identification of AHL-interacting proteins. We show that our new compounds are still recognised by different bacteria and that a novel biotin-tagged-AHL derivative interacts with a bacterial AHL receptor.

Relative C-capping propensities for nonpolar amino acids and the primary amide, which control helicity for many small peptides, have been determined by a new method. Practical consequences of the observed propensities and their temperature dependences are discussed.

We present an optimized procedure for the synthesis of (S)-vinylglycine from (S)-methionine. The key step is a solvent free pyrolysis of an intermediate sulfoxide at high temperature. Using our optimized reaction conditions, Cbz-protected vinylglycine was obtained in high yield and with almost no side products. The protocol is scalable, fast and avoids the use of poisonous reagents.

Adamantane scaffolds for affinity maturation of prostate cancer specific ligands of low molecular mass are described. These scaffolds are modular and can be used for conjugation of up to three ligands and an additional effector molecule by standard peptide coupling techniques. The potential of the scaffolds is demonstrated with the multimerization of GPI 1, a prostate cancer specific small molecule. A detailed study of multimerized GPI conjugates with near-infrared fluorophores and their binding properties to different prostate cancer cell lines shows the specific binding of these conjugates to cell types positive for prostate specific membrane antigen (PSMA). We demonstrate that these conjugates allow the sensitive imaging of prostate cancer cells with NIR methodology and suggest that our adamantane scaffolds might be generally useful for affinity maturation of small molecules targeting cell surface epitopes.

A general method to synthesize functionalized azabicyclo[X.3.0]alkane scaffolds 5 is reported. Key intermediates are azabicycloalkenes such as 1 and 2, which are acylated with unsaturated carboxylic acids and subsequently submitted to tandem olefin metathesis. The resulting bicyclic heterocycles are versatile intermediates for different dipeptide mimetics and can be used as intermediates for natural products with indolizidine scaffolds or analogues thereof.

[reaction: see text] A general method to synthesize bicyclic dipeptide mimetics is reported. Key intermediates are azabicycloalkenes 9 and 17, which are prepared via Diels-Alder reactions and subsequent mild deprotection. These unsaturated bicyclic heterocycles are versatile intermediates for different dipeptide mimetics of the aza- and diazabicycloalkane type, which is demonstrated by the synthesis of diazabicycloalkanes 11 and 19 in only 3-6 steps and good overall yield.

An efficient route to novel 1,3,5,7-tetrasubstituted derivatives of adamantane is described. This route starts from adamantane and gives the tetrafunctionalized derivative 9 in eight steps with an overall yield of 23%. These tetrahedrally shaped molecules possess three identical arms terminated by an activated carboxylic acid derivative and a protected amino function in the 1-position. We propose these tetravalent cage compounds such as 9 as scaffolds for the assembly of ligand/marker conjugates for studies of multivalent ligand receptor interactions. [reaction: see text]

We present the synthesis of new modular dipeptide mimetics based on diazabicycloalkane backbones. These diazabicycloalkanes are ligands for the prostate specific membrane antigen (PSMA), a well known tumor marker. Our previously described synthetic route to enantiomerically pure diazabicycloalkanes is extended to yield polyfunctional diazabicycloalkanes with a modular character using a new ring closing methodology. This, finally, allows us to attach linker moieties to different positions of the diazabicycloalkane scaffold providing conjugation sites to other functional molecules such as markers or cytostatic compounds. Furthermore, successful synthesis of sulphur-containing dipeptide analogues as for example CysX(AA)- or HCysX(AA)-mimetics on the basis of diazabicycloalkanes is described.

The selective targeting of a compound to tumors, or for that matter to any structure in the body, requires high stability of the compound in blood, biodistribution to the target site, adequate contact time with the target, adequate retention by the target, maintenance of drug potency, and adequate clearance of nontargeted compound. For over two decades, antibodies have been the scaffold of choice for delivering contrast agents and chemotherapeutics to tumor cells since they are stable in blood, typically have nanomolar affinities for their target, and, because binding and nonbinding domains are separated physically, tolerate substitution with contrast agents and chemotherapeutics. Although monoclonal antibodies (mAbs) are typically tolerant to the conjugation of chemotherapeutics, the agents themselves often lose potency in the conjugated form. Therefore, novel chemical strategies are required for releasing the cytotoxic agent, either after binding to the cancer cell surface or after endocytosis into the cell. A compelling example of this comes from the antitumor antibiotic calicheamicin. When conjugated to a tumor-targeting mAb through an amide linkage, the conjugate is accumulated by the tumor, but has no appreciable cytotoxicity. In contrast, when conjugated by using a pH-sensitive bifunctional linker that permits release of calicheamicin intracellularly (Figure 1), the conjugate shows potent antitumor activity. Indeed, gemtuzumab ozogamicin (“gem-ozo”, Mylotarg), a conjugate of a CD33-specific mAb and calicheamicin, which utilizes this bifunctional linker, is already approved for the treatment of certain acute myeloid leukemias. The taxanes are a class of potent chemotherapeutics that possess a complex chemical structure. Recently, two different strategies have been employed to conjugate taxanes to tumor-targeting monoclonal antibodies, while retaining chemotherapeutic potency. In conjugate mAb-1 (Scheme 1), an enzymatically cleavable glutarate ester bond is placed between the amide linkage to

The synthesis of PNA-monomers with variations in the substitution pattern using the Ugi-Reaction is described. The one-pot procedure leads to new totally protected PNA-monomers which can be selectively cleaved to N-protected monomeric building blocks for PNA synthesis.