Catalytic Enantioselective Reactions from Research to Application. Diarylmethanol-Containing Auxiliaries as a Study Case

Chiral auxiliaries – in the broadest possible definition of the term – can be obtained by Grignard reactions of Aryl-MgX with chiral esters R*CO2R. The products formed all contain a diarylmethanol structural moiety. They can be used in stoichiometric and catalytic enantioselective reactions, preferably as ligands on metal centers. They have also found applications for enantioselective inclusions, for solid-phase reactions, and for liquid-crystal preparations

6-Chloromethylierte 2-(tert-Butyl)-1,3-dioxan- und -1,3-dioxin-4-one aus (R)- oder (S)-4,4,4- Trichloro-3- hydroxybuttersaure

Enantiopure (2S,6R)-and (2R,6S)-2-(tert-butyl)-1,3-dioxan-3-ones (2 and 3, resp., cis-configuration) are prepared from each of the commercially available enantiomeric 4,4,4-trichloro-3-hydroxybutanoic acids and pivalaldehyde (52%, after crystallization). Bromination of 2 with NBS in CCl4 gives an unstable bromo-trichloro-dioxanone to which structure D is tentatively assigned. Passing a solution of the crude product D in Et2O through a column of acidic Al2O3, (S)-6-(bromodichloromethyl)-2-(tert-butyl)-1,3-dioxin-4-one (7) is formed (ca, 70% overall yield from 2 on a 50-mmol scale). Treatment of the crude D with Zn powder in Et2O leads to (S)-2-(tert-butyl)-6-(dichloromethyl)-1,3-dioxin-4-one (9, ca. 35% from 2 on a 20-mmol scale). Reductive dehalogenations of 2 and 7 with triphenyltin hydride can be carried out selectively to produce the (dichloromethyl)- and (chloromethyl)-dioxanones 5 and 6, resp., and the (dichloromethyl)-, (chloromethyl)-, and non-chlorinated dioxinones 9, 10, and 11, resp. (yields after distillation and chromatography 37–49%)

Reduction of Ketones with LiAlH4 Complexes of α,α,α\u27,α\u27-Tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs) A Combination of Enantioselective Reduction and Clathrate Formation with a Discussion of LAH Reagents Bearing C2-Symmetrical Ligands

A complex prepared from one equivalent each of LiAlH4, EtOH and a TADDOL (α,α,α\u27,α\u27-tetraaryl-1,3-dioxolane-4,5-dimethanol) reduces aryl alkyl ketones to sec. alcohols with enantiomer ratios (er) up to 96 : 4. The chiral LAH derivative is used in two-fold excess in THF solution and at dry ice temperatures. The ability of TADDOLs to form clathrates diastereoselectively can be exploited to increase the er of the initially formed alcohols by a simple modification of the work-up procedure and hence, products of very high en- antiopurity (er 99 : 1) can be isolated. When (7i,/i)-TADDOLs (from (ZiA)-tartrate) are applied in the reaction, the 1-aryl-alkanols formed preferentially have (S) configuration, as for the products obtained with the corresponding (P)-BINOL and (P)-BIPHENOL derivatives. A common mechanistic model is discussed

Grossansätze zur Herstellung von α,α,α',α'-Tetraaryl-1,3-dioxolan-4,5-dimethanolen (TADDOLe): Nützliche Hilfsstoffe für die EPC-Synthese und ihre Struktur im Festkörper

The large-scale preparation of α,α,α',α'-tetraaryl-1,3-dioxolan-4,5-dimethanol derivatives is described. It consists of acetalization of dimethyl tartrate and Grignard addition. The diols 2–12 thus obtained are crystalline and stable. They are useful as versatile auxiliaries for enantioselective reactions and for resolutions by clathrate formation. The X-ray crystal structure of the inclusion compound from one of the TADDOLs and CCl4 is described (6·2 CCl4) and compared with the structures of analogous derivatives, including C2-symmetrical diphosphines. Reference is given to other chiral auxiliaries containing the diaryl-methanol group

Biological and Pharmacokinetic Studies with β-Peptides

Interactions and cleavage reactions of β-amino acids and β-oligopeptides (up to nine residues, carrying the side chains of Ala, Val, Leu, Ile, Phe, Ser, Lys, and Hop) with biological systems, such as the most potent peptidases (pronase, proteinase K, 20S proteasome), microorganisms (Pseudomonas aeruginosa and Pseudomonas putida), and mammalian blood (intravenous application to rats) have been investigated and compared with ?-peptides. The results are: i) the three peptidases do not cleave β-peptides at all (within 24 h), and they are not inhibited by a β-peptide; ii) except for certain 3-aminobutanoic-acid (β-HAla) derivatives, neither free, nor N-acetyl-β-amino acids, nor β-peptides (offered as sole N and C source) lead to growth of the two bacteria tested; iii) two water-soluble β-heptapeptides (with Lys side chains) were shown to have elimination half-lives t1/2(β) of 3 and 10 h at 100- and 30-ng/ml levels, respectively, in the rodent blood – much larger than those of α-peptides. Thus, the preliminary results described here confirm the much greater stability of β-peptides, as compared to α-peptides, towards metabolization processes, but they also suggest that there may be interactions (by hitherto unknown mechanisms) between the worlds of α- and β-peptides

Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish

No abstract available

Lithium storage mechanisms in purpurin based organic lithium ion battery electrodes

Current lithium batteries operate on inorganic insertion compounds to power a diverse range of applications, but recently there is a surging demand to develop environmentally friendly green electrode materials. To develop sustainable and eco-friendly lithium ion batteries, we report reversible lithium ion storage properties of a naturally occurring and abundant organic compound purpurin, which is non-toxic and derived from the plant madder. The carbonyl/hydroxyl groups present in purpurin molecules act as redox centers and reacts electrochemically with Li-ions during the charge/discharge process. The mechanism of lithiation of purpurin is fully elucidated using NMR, UV and FTIR spectral studies. The formation of the most favored six membered binding core of lithium ion with carbonyl groups of purpurin and hydroxyl groups at C-1 and C-4 positions respectively facilitated lithiation process, whereas hydroxyl group at C-2 position remains unaltered

Crossing borders to bind proteins—a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation

Transesterification of PHA to Oligomers Covalently Bonded with (Bio)Active Compounds Containing Either Carboxyl or Hydroxyl Functionalities

© 2015 The Authors. Published by Public Library of Science. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0120149This manuscript presents the synthesis and structural characterisation of novel biodegradable polymeric controlled-release systems of pesticides with potentially higher resistance to weather conditions in comparison to conventional forms of pesticides. Two methods for the preparation of pesticide-oligomer conjugates using the transesterification reaction were developed. The first method of obtaining conjugates, which consist of bioactive compounds with the carboxyl group and polyhydroxyalkanoates (PHAs) oligomers, is "one-pot" transesterification. In the second method, conjugates of bioactive compounds with hydroxyl group and polyhydroxyalkanoates oligomers were obtained in two-step method, through cyclic poly(3-hydroxybutyrate) oligomers. The obtained pesticide-PHA conjugates were comprehensively characterised using GPC, 1H NMR and mass spectrometry techniques. The structural characterisation of the obtained products at the molecular level with the aid of mass spectrometry confirmed that both of the synthetic strategies employed led to the formation of conjugates in which selected pesticides were covalently bonded to PHA oligomers via a hydrolysable ester bond