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.
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.
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)
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.
