- Design and preparation of a novel prolinamide-based organocatalyst for the solvent-free asymmetric aldol reaction
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The preparation of four novel organocatalysts as highly diastereo and enantioselective catalysts for the solvent-free asymmetric aldol reaction was described. These organocatalysts were synthesized in eight steps applying simple and commercially available starting materials. The best results were obtained for the proline-derived catalyst, providing access to the desired adducts in up to 95% yield, 1:19 syn/anti and 98% e.e. Moreover, even sterically bulky aldehydes and substituted cyclohexanones were well tolerated. DFT calculations and control experiments indicated that several hydrogen bonding interactions between the aldehyde and the enamine intermediate are responsible for the stereoselective chiral induction process and that the trifluoroacetate counter-anion is crucial for the attainment of higher stereoselectivities.
- Martins, Rafaela de S.,Pereira, Mathias P.,de Castro, Pedro P.,Bombonato, Fernanda I.
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- Stereochemistry-Controlled Supramolecular Architectures of New Tetrahydroxy-Functionalised Amphiphilic Carbocyanine Dyes
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The syntheses of novel amphiphilic 5,5′,6,6′-tetrachlorobenzimidacarbocyanine (TBC) dye derivatives with aminopropanediol head groups, which only differ in stereochemistry (chiral enantiomers, meso form and conformer), are reported. For the achiral meso form, a new synthetic route towards asymmetric cyanine dyes was established. All compounds form J aggregates in water, the optical properties of which were characterised by means of spectroscopic methods. The supramolecular structure of the aggregates is investigated by means of cryo-transmission electron microscopy, cryo-electron tomography and AFM, revealing extended sheet-like aggregates for chiral enantiomers and nanotubes for the mesomer, respectively, whereas the conformer forms predominately needle-like crystals. The experiments demonstrate that the aggregation behaviour of compounds can be controlled solely by head group stereochemistry, which in the case of enantiomers enables the formation of extended hydrogen-bond chains by the hydroxyl functionalities. In case of the achiral meso form, however, such chains turned out to be sterically excluded.
- B?ttcher, Christoph,Cuellar-Camacho, Jose Luis,Haag, Rainer,Schade, Boris,Singh, Abhishek Kumar,Wycisk, Virginia,von Berlepsch, Hans
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supporting information
p. 6919 - 6934
(2020/06/01)
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- Synthesis of phosphonoglycine backbone units for the development of phosphono peptide nucleic acids
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A series of phosphono-modified backbone mimics based on achiral and chiral N-(dihydroxypropyl)glycine units were obtained by sequential addition of phosphonate and nucleobase moieties to suitably protected dihydroxypropylamines. Simple synthetic strategies enabled the preparation of various target derivatives that will be useful as building blocks for the preparation of new synthetic polymers containing a phosphonate internucleotide linkage in place of the standard phosphodiester bond. Copyright
- Doboszewski, Bogdan,Groaz, Elisabetta,Herdewijn, Piet
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p. 4804 - 4815
(2013/08/23)
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- Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics
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Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave Ki values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-d-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4- methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(±)-65 vs (±)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts.
- Clinch, Keith,Evans, Gary B.,Froehlich, Richard F.G.,Gulab, Shivali A.,Gutierrez, Jemy A.,Mason, Jennifer M.,Schramm, Vern L.,Tyler, Peter C.,Woolhouse, Anthony D.
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supporting information
p. 5181 - 5187
(2012/11/07)
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- ACYCLIC AMINE INHIBITORS OF 5'-METHYLTHIOADENOSINE PHOSPHORYLASE AND NUCLEOSIDASE
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The present invention relates to compounds of the general formula (I) which are inhibitors of 5'-methylthioadenosine phosphorylase or 5'-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5'-methylthioadenosine phosphorylase or 5'-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.
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Page/Page column 22; 23
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF PROTECTED DIHYDROXYPROPYL TRIALKYLAMMONIUM SALTS AND DERIVATIVES THEREOF
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A process for the preparation of protected dihydroxypropyl trialkylammonium salts, particularly in chiral form is described. In particular, a process for the preparation of (2,2-dimethyl-1,3-dioxolan-4-ylmethyl)trialkylammonium salts, particularly in chiral form is described. Furthermore, a process is described wherein the (2,2-dimethyl-1,3-dioxolan-4ylmethyl)trialkylammonium salts is a 2,2-dimethyl-1,3-dioxolan-4-ylmethyl trimethylammonium salt, preferably in chiral form. The protected dihydroxypropyl trialkylammonium salts lead to L-carnitine (9) when in chiral form (5).
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Page/Page column 7; 8; 9
(2008/06/13)
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- COMPOUNDS AND METHODS FOR TREATING TOLL-LIKE RECEPTOR 2-RELATED DISEASES AND CONDITIONS
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The present invention relates to compounds and methods useful in the prevention or treatment of diseases or conditions associated with Toll-like receptor 2 activation.
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- Synthesis of glycidol- and sugar-derived bicyclic β- and γ/δ-amino acids for peptidomimetic design
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Constrained bicyclic β- and γ/δ-amino acids using glycidol and sugar derivatives were developed. The synthetic strategies involved epoxide ring opening of a glycidol derivative, and subsequent coupling with sugar-derived amines, leading to di- or trisubst
- Danieli, Elisa,Trabocchi, Andrea,Menchi, Gloria,Guarna, Antonio
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p. 4372 - 4381
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF PROTECTED 3-AMINO-1,2-DIHYDROXYPROPANE ACETAL AND DERIVATIVES THEREOF
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A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.
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- Process for the preparation of protected 3-amino-1,2-dihydroxypropane acetal and derivatives thereof
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A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.
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- Efficient Pathways to (R)- and (S)-5-Hydroxymethyl-2-oxazolidinone and some Derivatives
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2-Oxazolidinones are a very interesting class of compounds due to their various pharmacological effects.Two new syntheses of enantiomerically pure (R)- and (S)-5-hydroxymethyl-2-oxazolidinone have been developed starting with D-mannitol, L-ascorbic acid and (R)- or (S)-malic acid. (R)- and (S)-5-hydroxymethyl-2-oxazolidinone have been used to synthesize some new homochiral 2-oxazolidinone derivatives.
- Danielmeier, Karsten,Steckhan, Eberhard
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p. 1181 - 1190
(2007/10/02)
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- The Synthesis of Biphenomycin B
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Biphenomycin B, a highly potent antibiotic against Gram-negative, β-lactam-resistant bacteria, which was previously isolated from culture filtrates of Streptomyces griseorubiginosus No. 43708, has now been synthesized.
- Schmidt, Ulrich,Meyer, Regina,Leitenberger, Volker,Lieberknecht, Albrecht,Griesser, Helmut
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p. 275 - 277
(2007/10/02)
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- Total synthesis of the biphenomycins; II. Synthesis of protected (2S,4R)-4-hydroxyornithines
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Improved synthetic methods for the preparation of three differently protected (2S,4R)-4-hydroxyornithine (10, 16, 24) have been developed which obviously can be used for the construction of the other stereoisomers. Formation of the corresponding α,β-dideh
- Schmidt,Meyer,Leitenberger,Stabler,Lieberknecht
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p. 409 - 413
(2007/10/02)
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- Syntheses and Structures of Diastereomerically Pure 2,6-Disubstituted 3-Morpholinones
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The syntheses of the hitherto unknown diastereomerically pure 2,6-disubstituted 3-morpholinones 17, 18, 21, 22, 23, and 24 are described.The necessary starting compounds, the optically active amino alcohols 6 and 12, are synthesized by improved or new procedures.A two-step synthetic sequence via the 2-chloro-N-(2-hydroethyl)carboxamides 15, 16, 19, and 20 leads to products much purer than those obtained by the known direct condensation of amino alcoholates with α-halogen carboxylic esters.The structures of the title compounds are characterized by their NMR spectra.
- Danklmaier, Johann,Hoenig, Helmut
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p. 1149 - 1154
(2007/10/02)
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