14316-06-4Relevant articles and documents
Chirality-sensing binaphthocrown ether-polythiophene conjugate
Fukuhara, Gaku,Inoue, Yoshihisa
, p. 7859 - 7864 (2010)
Abstract: An enantiomeric binaphthyl unit was tethered to adjacent thiophenes with oxyethylene linkers to give a chiral polythiophene with binaphthocrown ether cavities. Upon inclusion of a chiral cationic guest in the cavity of the chiral crown ether-polythiophene conjugate, the bithiophene unit was twisted to shorten the effective conjugation length of polythiophene backbone, enabling us to sense the guest binding by reading out the amplified optical signal gains arising from the backbone structure change. This strategy allowed us to discriminate the guest chirality without using chiroptical signals or a circular dichroism spectrometer to achieve the highest enantioselectivity of 7.3 for valine methyl ester with a 40-fold enhanced sensitivity compared with the corresponding monomeric sensor.
Synthesis of the C26-C32 Oxazole Fragment of Calyculin C: A Test Case for Oxazole Syntheses
Pihko, Petri M.,Koskinen, Ari M. P.
, p. 92 - 98 (1998)
The synthesis of the C26-C32 oxazole fragment 4 and its C32 epimer 20 of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C is presented. The syn methyl arrangement in 4 was established through cyclic stereocontrol. Several methods for oxidizing the intermediate oxazolines 18 and 19 to the finished oxazole fragments were explored. The best results were obtained with oxidations proceeding through the corresponding ester enolate when the carbamate NH side chain was temporarily protected with a TMS group, or with CuBr2/DBU/HMTA-based oxidations. The finished oxazole fragment 4 was obtained in 21% overall yield, starting from Boc-D-alaninal.
New helical folds in α-peptides with alternating chirality
Sharma, Gangavaram V. M.,Venkateshwarlu, Gajulapati,Reddy, Pothula Purushotham,Kunwar, Ajit C.
, p. 11428 - 11438 (2014)
In α-peptides, the 8/10 helix is theoretically predicted to be energetically unstable and has not been experimentally observed so far. Based on our earlier studies on 'helical induction' and 'hybrid helices', we have adopted the 'end-capping' strategy to induce the 8/10 helix in α-peptides by using short α/β-peptides. Thus, α-peptides containing a regular string of α-amino acids with alternating chirality were end capped by α/β-peptides with 11/9-helical motifs at the termini. Extensive NMR spectroscopy studies of these peptides revealed the presence of a hitherto unknown 8/10-helical pattern; the H-bonds in the shorter pseudorings were rather weak. The approach of using short helical motifs to induce new mixed helices in α-peptides could provide avenues for more versatile design strategies. A new twist: α-Peptides containing a regular string of α-amino acids with alternating chirality were end capped by α/β-peptides with 11/9-helical motifs at the termini. Extensive NMR spectroscopy studies of these peptides revealed the presence of a hitherto unknown 8/10-helical pattern in this hybrid helix (see figure); the H-bonds in the shorter pseudorings were rather weak. The addition of helix-stabilizing influences may enhance the propensity and stability of these uncommon folding patterns in oligomers of α-amino acids.
Rhodium-Catalyzed Enantioselective Synthesis of Oxazinones via an Asymmetric Ring Opening-Lactonization Cascade of Oxabicyclic Alkenes
Yen, Andy,Pham, Anh Hoang,Larin, Egor M.,Lautens, Mark
supporting information, p. 7549 - 7553 (2019/10/02)
The rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes is shown to be an efficient method for synthesizing chiral heterocycles. We demonstrate that the pairwise combination of chiral catalyst with chiral amino-acid-derived pronucleophiles results in a stereodivergent synthesis of diastereomeric hydroxyesters. A favorable conformational preference induces the subsequent lactonization of one diastereomer leading to the highly enantioselective synthesis of oxazinones.
A valsartan synthesis method of alkylation impurity (by machine translation)
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Paragraph 0016; 0017, (2018/10/19)
A valsartan synthesis method of alkylation impurities, is to L - valine that may exist in the impurity D - valine, alanine, leucine isoleucine amino acid as the raw material and the like, in thionyl chloride under the conditions of the esterification reaction with methanol, after the reaction by reducing pressure methanol, then with 2 - cyano - 4' - bromomethyl biphenyl in the reaction under alkaline conditions, after completion of the reaction, saturated salt water washing, adding hydrochloric acid to adjust the pH=1 - 2, the temperature of the crystallization, filtering to obtain the target product valsartan alkylation impurity. The present invention is to provide high-purity impurity, will its known impurity used for alkylation of valsartan in mass analysis, the position of the clear of impurities in the sample, the degree of impurity of the sample inspection, optimizes the analytical method, contribute to improving the quality of valsartan research, for the production of valsartan reducing impurity, improve the quality of the valsartan; at the same time, this invention has mild condition, the reaction yield is higher, convenient operation and the like. (by machine translation)
Synthesis method for nitro group-containing natural product chrysamides B and diastereoisomer-compound thereof
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Paragraph 0024; 0025, (2018/11/22)
The invention belongs to the technical fields of medicinal chemistry and organic synthesis, and relates to a synthesis method for a nitro group-containing natural product chrysamides B, a chrysamidesB diastereoisomer-compound and a synthesis method and application thereof. According to the invention, a convergent synthesis method is adopted to condense chiral epoxy carboxylic acid and chiral dimethylpiperazine ring, and thereby the nitro group-containing natural product chrysamides B with a symmetrical structure and the chrysamides B diastereoisomer-compound are easily and efficiently synthesized. By three-step continuous oxidation, chiral epoxy carboxylic acid is prepared from p-nitrobenzaldehyde which is easy to obtain commercially, and dimethylpiperazine ring is prepared by reduction after alanine dimerization. The compound shows inhibitory activity on pasteurella multocida. Such a convergent synthesis route can be applied to the chemical synthesis of compounds with the similar structure and related derivatives, opening up a broad development space for novel antibiotic drugs.
NR2B SELECTIVE NMDA-RECEPTOR ANTAGONISTS FOR TREATMENT OF IMMUNE-MEDIATED INFLAMMATORY DISEASES
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Paragraph 200; 230, (2017/03/21)
The present invention provides novel means and methods for treatment auf immunemediated inflammatory diseases.
Chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes as novel σ1 receptor ligands
Fanter, Lena,Müller, Christoph,Schepmann, Dirk,Bracher, Franz,Wünsch, Bernhard
, p. 4778 - 4799 (2017/10/05)
Starting from enantiomerically pure amino acids, 1,4-diazepanes with various substituents in 1, 2, and 4-position were synthesized following the late stage diversification strategy. The key step in the formation of the seven-membered ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The configuration in 2-position does not influence the σ1 affinity and selectivity over related receptors. A cyclohexylmethyl or a butyl group are the preferred substituents in 4-position, whereas a methyl moiety in 2-position and a (substituted) benzyl moiety in 1-position result in the highest σ1 affinity. These results fit nicely to the reported σ1 pharmacophore models. The compounds did not inhibit the structurally related fungal enzyme sterol Δ8,7-isomerase, but showed inhibition of diverse enzymes in late cholesterol biosynthesis at high concentrations. In a screening against more than 50 target proteins, (2S)-1-benzyl-4-(4-methoxybenzyl)-2-methyl-1,4-diazepane ((S)-28b, Ki(σ1) = 0.86 nM) showed a clean receptor profile. The dose dependent potentiation of electrically stimulated contractions of guinea pig vas deferens indicates σ1 agonistic activity of (S)-28b. Even at a dose of 100 mg/kg (S)-28b did not induce severe toxic or behavioral effects in the Irwin screen. Clear cognition enhancing effects were observed for (S)-28b after inducing amnesia by scopolamine.
Benzoxaborole Antimalarial Agents. Part 5. Lead Optimization of Novel Amide Pyrazinyloxy Benzoxaboroles and Identification of a Preclinical Candidate
Zhang, Yong-Kang,Plattner, Jacob J.,Easom, Eric E.,Jacobs, Robert T.,Guo, Denghui,Freund, Yvonne R.,Berry, Pamela,Ciaravino, Vic,Erve, John C. L.,Rosenthal, Philip J.,Campo, Brice,Gamo, Francisco-Javier,Sanz, Laura M.,Cao, Jianxin
, p. 5889 - 5908 (2017/07/22)
Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mice, rats, and dogs. It was highly active against the other 11 P. falciparum strains, which are mostly resistant to chloroquine and pyrimethamine. The rapid parasite in vitro reduction and in vivo parasite clearance profile of 46 were similar to those of artemisinin and chloroquine, two rapid-acting antimalarials. It was nongenotoxic in an Ames assay, an in vitro micronucleus assay, and an in vivo rat micronucleus assay when dosed orally up to 2000 mg/kg. The combined properties of this novel benzoxaborole support its progression to preclinical development.
Ferrocene-modified amino acids: synthesis and in vivo bioeffects on hippocampus
Rodionov,Snegur,Simenel,Dobryakova, Yu. V.,Markevich
, p. 136 - 142 (2017/07/05)
A method for the ferrocene modification of amino acids of natural and synthetic origin has been developed. In the in vivo studies, the hippocampal electrical activity under the action of ferrocenyl(phenylpyrazolyl)glycine (1) was assessed. A meaningful rise (up to 25% compared to the control) in the response amplitudes of the focal potentials of the hippocampal region СА1 after intraperitoneal administration of compound 1 at the dose of 2.0 mg kg–1 was established.
