Electrogenic transport by lipophilic guanidinium salts as anion carriers in bilayer membranes

Anion transport by four isomers of tetradecylguanidinium in vesicle bilayer membranes was investigated by ion-selective electrode and pH-sensitive fluorescence methods. On a macroscopic scale, these carriers mediate hydroxide-anion antiport. In the absence of an externally imposed ionic gradient, the carriers produce a pH gradient due to rapid partition-deprotonation of the carrier and diffusion of the guanidine conjugate base. The formally coupled anion transport is slow relative to this process, and the system exhibits a corresponding membrane polarisation detected with potential-sensitive fluorescent dyes. Selective anion transport in competition with the efficient hydroxide transport is detected only with relatively easily extracted anions and N,N′-disubstituted isomers. Membrane polarisation changes can be deduced from simple equivalent circuits derived from the Goldman–Hodgkin–Katz voltage equation.     

Enantioselective sensing of lactate by pyridinium-based chiral receptor

A simple pyridinium-based chiral receptor 1 containing l-valine as the chiral source has been designed and synthesized. The receptor 1 fluorometrically recognizes d-lactate over l-lactate in CH₃CN with an enantiomeric fluorescence ratio (ef) of 5.32.     

Enantioselective synthesis of a dual orexin receptor antagonist

A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. Key features of the synthesis include a mild copper-catalyzed amination, a highly chemoselective conjugate addition, and a tandem enantioselective transamination/seven-membered ring annulation. The synthesis requires inexpensive starting materials and only four linear steps for completion.     

Enantioselective nanofiber-spinning of chiral calixarene receptor with guest

Chiral para-tert-butylcalix[4]arene bearing (S)-alpha-methylbenzylamine groups at lower rim only self-assembles with one of two enantiomers of 2,3-dibenzoyltartaric acid into coiled nanofibers and the coiled nanofibers only stack with the nanofibers having the same handedness to construct bigger ribbon-like fibers bearing porosity.     

Enantioselective DNA alkylation by a pyrrole-imidazole S-CBI conjugate

Conjugates 12S and 12R of N-methylpyrrole (Py)-N-methylimidazole (Im) seven-ringed hairpin polyamide with both enantiomers of 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) were synthesized, and their DNA alkylating activity was examined. High-resolution denaturing gel electrophoresis revealed that 12S selectively and efficiently alkylated at one match sequence, 5'-TGACCA-3', in 450-bp DNA fragments. The selectivity and efficiency of the DNA alkylation by 12S were higher than those of the corresponding cyclopropapyrroloindole (CPI) conjugate, 11. In sharp contrast, another enantiomer, 12R, showed very weak DNA alkylating activity. Product analysis of the synthetic decanucleotide confirmed that the alkylating activity of 12S was comparable with 11 and that 12S had a significantly higher reactivity than 12R. The enantioselective reactivity of 12S and 12R is assumed to be due to the location of the alkylating cyclopropane ring of the CBI unit in the minor groove of the DNA duplex. Since the CBI unit can be synthesized from commercially available 1,3-naphthalenediol, the present results open up the possibility of large-scale synthesis of alkylating Py-Im polyamides for facilitating their use in future animal studies.     

Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst

[reaction: see text] The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give beta-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).     

Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair

The first enantioselective tungstate‐catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug‐like phenyl and heterocyclic sulfides under mild conditions with H₂O₂, a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)‐Lansoprazole, a commercial proton‐pump inhibitor. The active ion‐pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies.     

The reversal by sulfate of the denaturant activity of guanidinium

Guanidinium (Gdm+) chloride is a powerful protein denaturant, whereas the sulfate dianion (SO42-) is a strong stabilizer of folded protein states; Gdm2SO4 is effectively neutral in its effects on protein stability. While the "neutralizing" effects of protein-stabilizing solutes on the activity of denaturants can be broadly interpreted in terms of additive effects of the solutes, recent experimental and simulation studies support a role for hetero-ion interactions in the effect of sulfate on Gdm+ denaturation [Mason, P. E.; et al. J. Phys. Chem. B 2005, 109, 24185-24196]. Here we describe an experimental strategy for testing this mechanism that involves spectroscopic analysis of the separate effects of alkali metal sulfates (Na2SO4, Rb2SO4), GdmCl, and Gdm2SO4 on the folded populations of several peptides chosen to dissect specific noncovalent contributions to the conformational stability of proteins [alanine-based helical peptides stabilized by hydrogen bonds, tryptophan zipper (trpzip) peptides stabilized largely by cross-strand indole-indole interactions]. While the trpzip peptides are highly sensitive to GdmCl denaturation, they are unaffected by NaCl, Na2SO4, or Gdm2SO4, indicating that the reversal of the denaturant activity of Gdm+ by sulfate in this case is not due to competing stabilizing (sulfate) and destabilizing (Gdm+) interactions. Gdm2SO4 was found to retain considerable denaturant activity against alanine-based alpha-helical peptides. The differences in the effects of Gdm2SO4 on the two peptide types can be understood in terms of the different mechanisms of Gdm+ denaturation of trpzip peptides and helical peptides, respectively, and the specific nature of Gdm+ and SO42- ionic "clustering" that differentially affects the ability of Gdm+ to make the molecular interactions with the peptides that underlie its denaturant activity.     

Androgen receptor antagonists and anti-prostate cancer activities of some synthesized steroidal candidates

In continuation of our previous work, a novel series of steroid derivatives were synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Twenty-one heterocyclic derivatives containing a cyanopyrane ring fused to a steroidal moiety were conveniently synthesized and screened for their antagonistic, antiandrogen and prostate anticancer activities comparable to that of bicalutamide as the reference control. Some of the compounds exhibited better antagonistic, antiandrogen and prostate anticancer activities than the reference controls. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). Synthetic steroidal structures fused to a substituted cyanopyrane ring seem to be a promising approach in the search for novel leads for potent antagonistic, antiandrogen and prostate anticancer agents.     

Direct aldol reactions catalyzed by a heterogeneous guanidinium salt/proline system under solvent-free conditions

The combined activity of (S)-proline and an achiral cocatalyst (a TBD-derived guanidinium salt) allow direct aldol reactions to be carried out with high diastereoselectivity and enantioselectivity under solvent-free conditions with a rather simple reaction setup where stirring is not required.     

Enantioselective chromenone benzoxazole receptor for glutamic acid and its derivatives

Combination of a binaphthyl unit with chromenone benzoxazole fragments provided a chiral receptor that is enantioselective for glutamic acid and its derivatives. The receptor racemic mixture was resolved by TLCs impregnated with (R,R)-thiodilactic acid. High association constants were measured for dansylglutamic acid, using a fluorescent method. This receptor can be used for the resolution of the tosylglutamic acid racemic mixture.     

Enantioselective alkenylation and phenylation catalyzed by a chiral CuF complex

A new method for CuF-catalyzed alkenylation and phenylation of aldehydes and an activated ketone using air- and moisture-stable alkenylsilanes and phenylsilane as a nucleophile is described. This methodology was extended to highly enantioselective catalytic alkenylation and phenylation using DTBM-SEGPHOS as a chiral ligand. Substrate generality is broad, and an alkenylsilane with a long alkyl chain and an internal alkenylsilane can be also used as a nucleophile. The key to success partly involves the accelerated regeneration of reactive alkenylcopper and phenylcopper through transmetalation from the silylated nucleophiles, and stabilization of the reactive copper reagents, both of which are effected by the diphosphine ligands.     

Enantioselective cyanosilylation of ketones catalyzed by a chiral oxazaborolidinium ion

The chiral oxazaborolidinium salt 1 (X = TfO) is an excellent catalyst for the cyanosilylation of methyl ketones promoted by trimethylsilyl cyanide and diphenylmethyl phosphine oxide as co-reactants (to generate Ph(2)MePOTMS(N=C:) as a reactive intermediate). The face selectivity of this reaction parallels that previously observed for the corresponding reaction of aldehydes. A unifying and rational mechanistic explanation is provided for these enantioselective reactions. Evidence is presented to support the importance of alpha-C-H...O hydrogen bonding, pi,pi-interaction of the complexed ketonic carbonyl with the mexyl group of 1, and an early transition state for high enantioselectivity. The cyanosilylation reaction described herein provides access to many useful chiral compounds.     

Enantioselective hydrogenation of alkenes and imines by a gold catalyst

A new neutral dimeric gold(I) complex bearing the 1,2-bis[(2R,5R)-2,5-dimethylphospholanebenzene] [(R,R)-Me-Duphos] ligand has been synthesized which catalyzes the asymmetric hydrogenation of alkenes and imines under mild reaction conditions.     

Enantioselective Staudinger synthesis of beta-lactams catalyzed by a planar-chiral nucleophile

The development of efficient methods for the stereoselective generation of beta-lactams is an important goal, due to their biological activity and their utility as synthetic intermediates. The Staudinger reaction, an overall [2 + 2] cycloaddition of a ketene with an imine, provides a nicely convergent route to this family of compounds. Nearly all studies to date of asymmetric variants of the Staudinger reaction have focused on the use of chiral auxiliaries to control the stereochemistry of the beta-lactam. In this report, we establish that a planar-chiral derivative of 4-(pyrrolidino)pyridine serves as a very effective enantioselective catalyst for the Staudinger beta-lactam synthesis, coupling a range of symmetrical and unsymmetrical ketenes with an array of imines with very good stereoselection and yield.