Various aspects of enantiomeric recognition of (S,S)-dimethylpyridino-18-crown-6 by several organic ammonium salts

Abstract

Factors responsible for complex stability and enantiomeric recognition for the interactions of (S,S)-dimethylpyridino-18-crown-6 with several organic ammonium salts were examined using an ¹H NMR technique. The results indicate that cation structures have a significant effect on enantiomeric recognition; solvents play a very important role in the stability of the complexes, and anions can compete with ligands for the ammonium cations.     

The preparation of new chiral diphenyl-substituted macrocyclic polyether-diester compounds and their enantiomeric recognition of chiral organic ammonium salts

A series of chiral diphenyl-substituted macrocyclic polyether-diester ligands have been prepared from the chiral diphenyl-substituted tetraethylene glycol. Enantiomeric recogntion by the chiral diphenyl-substituted pyridino-diester-18-crown-6 compound ( 7 ) was studied by temperature dependent ¹H NMR spectroscopy in deuteriodichloromethane. This ligand exhibited chiral recognition when complexed with the hydrogen per-chlorate salts of (R)- and (S)-α-(1-naphthyl)ethylamine and (R)- and (S)-methyl phenylalaninate.     

A structural analysis of the complexes of (S,S)-dimethylpyridino-18-crown-6 with (R) and (S)-[α-(1-naphthyl)ethyl]ammonium perchlorate by NMR techniques and molecular modeling

Significant - interaction is found in the complexes of (S, S)-dimethylpyridino-18-crown-6 with (R)- and (S)-[-(1-naphthyl)ethyl]ammonium perchlorate. This finding is supported by the¹H NOESY NMR spectral technique, greater chemical shift changes of aromatic protons in both host and guest molecules upon complexation, and by molecular mechanics calculations. Because of the flexibility of the ligand, the tripod hydrogen bonding causes¹³C relaxation times of all periphery carbons to decrease without significant selectivity. Rotational energy barrier calculations of the methyl groups of the complexed ligand also show that the (S, S)-host-(R)-guest is the more stable complex.     

Enantiomeric recognition and separation of chiral organic ammonium salts by chiral pyridino-18-crown-6 ligands

Abstract

Optically pure allyloxy and dimethyl-substituted pyridino-18-crown-6 (8) was attached to silica gel by the following reactions. 4-Allyloxy-2,6-pyridinedimethyl ditosylate (23) was first prepared from chelidamic acid. Ditosylate 23 was treated with (S,S)-dimethyl-substituted tetraethylene glycol to form 8. Ligand 8 was treated with triethoxysilane using a platinum catalyst. The resulting chiral crown-substituted triethoxysilane 32 was reacted with silica gel in toluene at 90 C to attach the crown to silica gel. Preliminary results of the separation of [α-(1-naphthyl)ethyl]ammonium perchlorate into its (R) and (S) forms using the bound chiral crown with acetone/methanol (7/3) (v/v) as the eluant are reported. The preparation of chiral dimethyl(allyloxyphenyl)pyridino-18-crown-6 (9) that could be attached to silica gel on the side opposite to the pyridine ring is also reported.     

Chiral Tetraamines Based on (S)-2-(Aminomethyl)pyrrolidine: Template synthesis and properties of copper(II) complexes

The template reaction of {bis[(S)-2-(aminomethyl)pyrrolidine]}copper(II) with formaldehyde, nitroethane, and base in MeOH yields optically pure {1,7-bis[(S)-pyrrolidin-2-yl]-4-methyl-4-nitro-2,6-diazaheptane}- copper(II) ([Cu((S,S)-mnppm)]²⁺) in high yield. The same reaction with rac-2-(aminomethyl)pyrrolidine is also described. Preparative details and spectroscopic and electrochemical properties of the Cu^II complexes and of the free ligands are reported and compared with structural, spectroscopic and electrochemical data of the Cu^II complex of the unsubstituted parent ligand 1,7-bis[(S)-pyrrolidin-2-yl]-2,6-diazaheptane (ppm). The crystal structure of [Cu(ppm)]Cl ClO₄ has been determined by X-ray diffraction methods.     

Synthesis and stereochemistry of the (9S,13S,14S)-3-hydroxy-17-methylmorphinan-10-ols

O-Demethylation of (9S,13S,14S)-3-methoxy-17-methylmorphinan-10-one ( 2 ) to (9S,13S,14S)-3-hydroxy-17-methylmorphinan-10-one ( 3 ) and reduction of 3 to 10α- and 10β-hydroxylated morphinans 4 and 5 , are described. The stereochemistry of these epimeric alcohols was established on the bases of ¹H nmr data.     

Syntheses and structures of three chiral complexes derived from nucleophilic addition of L-proline to di-2-pyridyl ketone

In the presence of nickel acetate, a chiral ligand, (S)-Hdphp ((S)-N-[di(2-pyridyl)-hydroxy-methyl]-proline), was synthesized in situ by nucleophilic addition of L-proline to di-2-pyridyl ketone. Based on this ligand, three chiral mononuclear complexes, {Ni[(S)-dphp](DMF)(H₂O)}(ClO₄) (1), {Ni[(S)-dphp](H₂O)₂}(ClO₄)(H₂O)_1.5 (2), and {Ni[(S)-dphp](SCN)(H₂O)} (3), have been obtained and characterized by single-crystal X-ray diffraction, elemental analyses, and infrared spectra. By virtue of charge-assisted O–H?···?O hydrogen-bonding interactions, all the complexes possess double chain structures. The double chains were connected into 2-D networks via π?···?π stacking and CH?···?π interactions in 1. For 2, O–H?···?O hydrogen-bonding interactions between free water molecules and other oxygens as well as π?···?π stacking and CH?···?π interactions extend the chains into a 3-D network. Complex 3 exhibits 3-D structure via O–H?···?S interactions.     

The complete 1H and 13C chemical shift assignments of a cyclopropylpyrroloindole analog: Adozelesin

The ¹H and ¹³C nmr spectral assignments of [7bR]-N-[2-[(4,5,8,8a-tetrahydro-7-methyl-4-oxocyclo-propa[c]pyrrolo[3,2-e]indol-2(1H)-ylcarbonyl]-1H-indol-5-yl]-2-benzofurancarboxamide (Adozelesin) (1) are described. Complete and unambiguous assignments of the hydrogen and carbon spectra were made using a combination of conventional homonuclear and gradient-selected inverse-detected heteronuclear nmr experiments: double quantum filtered ¹H-¹H correlation spectroscopy (COSY), gradient-selected heteronuclear single quantum coherence spectroscopy (gs-HSQC), and gradient-selected heteronuclear multiple bond coherence spectroscopy (gs-HMBC). The enhanced sensitivity of these experiments allowed a smaller sample concentration and shorter spectral collection times for a full nmr analysis of this compound. The nmr data corroborates the published structure of this compound.     

α‐Propargyl amino acid‐derived optically active novel substituted polyacetylenes: Synthesis,secondary structures,and responsiveness to ions

Novel optically active substituted acetylenes HC? CCH₂CR¹(CO₂CH₃)NHR² [(S)‐/(R)‐ 1 : R¹ = H, R² = Boc, (S)‐ 2 : R¹ = CH₃, R² = Boc, (S)‐ 3 : R¹ = H, R² = Fmoc, (S)‐ 4 : R¹ = CH₃, R² = Fmoc (Boc = tert‐butoxycarbonyl, Fmoc = 9‐fluorenylmethoxycarbonyl)] were synthesized from α‐propargylglycine and α‐propargylalanine, and polymerized with a rhodium catalyst to provide the polymers with number‐average molecular weights of 2400–38,900 in good yields. Polarimetric, circular dichroism (CD), and UV–vis spectroscopic analyses indicated that poly[(S)‐ 1 ], poly[(R)‐ 1 ], and poly[(S)‐ 4 ] formed predominantly one‐handed helical structures both in polar and nonpolar solvents. Poly[(S)‐ 1a ] carrying unprotected carboxy groups was obtained by alkaline hydrolysis of poly[(S)‐ 1 ], and poly[(S)‐ 4b ] carrying unprotected amino groups was obtained by removal of Fmoc groups of poly[(S)‐ 4 ] using piperidine. Poly[(S)‐ 1a ] and poly[(S)‐ 4b ] also exhibited clear CD signals, which were different from those of the precursors, poly[(S)‐ 1 ] and poly[(S)‐ 4 ]. The solution‐state IR measurement revealed the presence of intramolecular hydrogen bonding between the carbamate groups of poly[(S)‐ 1 ] and poly[(S)‐ 1a ]. The plus CD signal of poly[(S)‐ 1a ] turned into minus one on addition of alkali hydroxides and tetrabutylammonium fluoride, accompanying the red‐shift of λ_max. The degree of λ_max shift became large as the size of cation of the additive. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Asymmetric anionic polymerization of optically active N-1-cyclohexylethylmaleimide

Chiral (S)-(−)-N-1-cyclohexylethylmaleimide [(S)-CEMI] and (R)-(+)-N-1-cyclohexylethylmaleimide [(R)-CEMI] were synthesized successfully and then polymerized with chiral complexes of (−)-sparteine or (S,S)-(1-ethylpropylidene)bis(4-benzyl-2-oxazoline) [(S,S)-Bnbox] and organometal as initiators in toluene or tetrahydrofuran to obtain optically active polymers. The effects of the polymerization conditions on the optical activity and structure of poly(N-1-cyclohexylethylmaleimide)s were investigated with gel permeation chromatography, circular dichroism, specific rotation, and ¹³C NMR measurements. Poly[(R)-CEMI] obtained with dimethylzinc (Me₂Zn)/(S,S)-Bnbox had the highest specific rotation ([α]₄₃₅ = +323.7°). Complexes of Bnbox and diethylzinc or Me₂Zn were used very effectively as chiral initiators for the asymmetric anionic polymerization of (S)-CEMI and (R)-CEMI. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4682–4692, 2004     

Enantioselectivity and cis/trans-Selectivity in Dirhodium(II)-Catalyzed addition of diazoacetates to olefins

The Rh¹¹-catalyzed carbenoid addition of diazoacetates to olefins was investigated with [Rh₂{(4S)-phox}₄] ( 1 ;phox = tetrakis[(4S)-tetrahydro-4-phenyloxazol-2-one]), [Rh₂{(2S)-mepy}₄] ( 2 ; mepy = tetrakis[methyl (2S)-tetrahydro-5-oxopyrrole-2-carboxylate]), and [Rh₂(OAc)₄] ( 3 ). While catalysis with 2 and 3 afford preferentially trans-cyclopropanecarboxylates, the cis-isomers are the major products with 1 . In general, the enantioselectivities achieved with 1 and 2 are comparable. Additions catalyzed by 1 are strongly sensitive to steric effects. Highly substituted olefins afford cyclopropanes in only poor yield. The preferential cis-selectivity observed in reactions catalyzed by 1 is attributed to dominant interactions between the ligand of the catalyst and the substituents of both olefin and diazoacetate, which overrule the steric interactions between olefin and diazoacetate in the transition state for carbene transfer.     

Crystallographic evidence of Gly‐d,l‐Met oxidation to its sulfoxide in the presence of gold(III): solid solution of the racemic mixture of two diastereoisomers

Crystallographic analysis of a solid solution of two diastereoisomers, i.e. ({(1S,R)‐1‐carboxy‐3‐[(R,S)‐methylsulfinyl]propyl}aminocarbonyl)methanaminium tetrachloridoaurate(III) and ({(1S,R)‐1‐carboxy‐3‐[(S,R)‐methylsulfinyl]propyl}aminocarbonyl)methanaminium tetrachloridoaurate(III), (C₇H₁₅N₂O₄S)[AuCl₄], has shown that in the presence of gold(III), the methionine part of the Gly‐d ,l ‐Met dipeptide is oxidized to sulfoxide, and no coordination to the Au^III cation through the S atom of the sulfoxide is observed. In view of our observation, literature reports that methionine acts as an N,S‐bidentate donor ligand forming stable gold(III) complexes require verification. Moreover, it has been demonstrated that crystallization of the oxidation product leads to a substantial 77:23 excess of both S‐methionine/R‐sulfoxide and R‐methionine/S‐sulfoxide over S‐methionine/S‐sulfoxide and R‐methionine/R‐sulfoxide. The presence of two different diastereoisomers at the same crystallographic site is a source of static disorder at this site.     

Accurate Structure and Bonding Description of the Transition Metal‐Disulfur Monoxide Complexes [(PMe3)2M(S2O)] (M = Ni,Pd, Pt): Grimme Dispersion Corrected DFT Study

Geometry and bonding energy analysis of M–S₂O bonds in the metal‐disulfur monoxide complexes [(PMe₃)₂M(S₂O)] of nickel, palladium, and platinum were investigated at DFT, DFT‐D3, and DFT‐D3(BJ) methods using three different functionals (BP86, PBE, and TPSS). The TPSS/DFT‐D3(BJ) yields better geometry, while the BP86 geometry is least accurate for studied complexes. The geometry of platinum complex optimized at TPSS/DFT‐D3(BJ) level is in excellent agreement with the available experimental values. The M–S bonds are shorter than the M–S(O) bonds. The Mayer bond orders suggest the presence of M–S and M–S(O) single bonds. Both the M–S and M–S(O) bond lengths vary with the density functionals as TPSS‐D3(BJ) < TPSS < PBE < BP86. The Hirshfeld charge distribution indicates that the overall charge flows from metal fragment to [S₂O]. The Ni–S₂O bond has greater degree of covalent character than the ionic. The contribution of dispersion interactions is large in computing accurate bond dissociation energies between the interacting fragments. The BDEs are largest for the functional TPSS and smallest for the functional BP86. The DFT‐D3 dispersion corrections to the BDEs between the metal fragments [(PMe₃)₂M] and ligand fragment [(S₂O)] for the TPSS functional are in the range 7.1–7.3 kcal · mol^–1, which are smaller than the corresponding DFT‐D3(BJ) dispersion corrections (9.4–10.6 kcal · mol^–1).     

Synthesis and characterization of platinum and palladium pyrrolidinedithiocarbamate complexes

Treatment of (PPh₃)₂MCl₂ (M = Pd or Pt) with ammonium pyrrolidinedithiocarbamate (NH₄S₂CNC₄H₈) in a 1:1 molar ratio gave (PPh₃)M(Cl)(κ ² S,S-S₂CNC₄H₈) [M = Pt (1), Pd (2)]. On the other hand, the interaction of these compounds in a 1:2 [M:L] molar ratio gave (PPh₃)Pt(κS-S₂CNC₄H₈)(κ ² S,S-S₂CNC₄H₈) (3), which contains both terminal and chelated dithiocarbamato ligands, or a yellow insoluble solid for M = Pd. The bis(diphenylphosphino)ethane platinum or palladium dichlorides [(dppe)MCl₂] reacted with the same ligand to give the salts [(dppe)M(κ ² S,S-S₂CNC₄H₈)]Cl (M = Pt (4), Pd (5) which have only one chelating dithiocarbamato ligand. The new compounds were characterized by ¹H-, ¹³C{¹H}- and ³¹P-n.m.r. spectroscopy, mass spectrometry, elemental analysis and X-ray single crystal structure analysis.     

Synthesis,characterization, CT-DNA binding and docking studies of novel selenated ligands and their palladium complexes

A novel selenated Schiff base (S) -L ¹ H has been synthesized from (2S)-1-(benzylselanyl)-3-phenylpropan-2-amine which upon reduction formed a reduced Schiff base (S) -L ² H . Palladium (II) complexes (S) -1 and (S) -2 of ligands (S) -L ¹ H and (S) -L ² H respectively were successfully synthesized. The structures of all four compounds were thoroughly identified by analytical and various spectroscopic techniques. The absolute molecular structures of the above two complexes were further confirmed by single crystal X-ray diffraction. Both (S) -L ¹ H and (S) -L ² H coordinated as monobasic ((S) -L ^1–2 ), chelating, tridentate (Se,N,O⁻) ligands resulting in the complexes of composition (S) - [PdCl( L ^1/2 )] [(S) -1/2 ]. In the crystals of complexes (S) -1 and (S) -2 , there were moderate to strong Se⋯O, CH⋯Cl and CH⋯O types of intermolecular secondary interactions. CT-DNA binding activity of these selenium-containing ligands and their palladium complexes bearing a Pd–Se bond have been evaluated for the first time by performing electronic absorption titration and fluorescence emission quenching using CT-DNA-EB and viscometric experiments. These ligands and complexes exhibited remarkable DNA binding activity as shown by their intrinsic DNA binding constants (K_b) and Stern–Volmer constants (K_sv) in the ranges 5.2–9.9 × 10⁴ and 3.6–4.7 × 10⁴, respectively. The viscosity of CT-DNA decreases with increasing concentration of these compounds. The results of the DNA-binding studies revealed that all of the compounds interact with DNA at a minor groove which was further confirmed by molecular docking studies.     

Enantioseparation of racemic organic ammonium perchlorates by a silica gel bound optically active di-tert-butylpyridino-18-crown-6 ligand

Both enantiomers of the novel chiral di-tert-butylpyridino-18-crown-6 ligand (R,R)-7 and (S,S)-7 containing an allyloxy group on the pyridine subcyclic unit were prepared by the reaction of 4-allyloxy-2,6-pyridinedimethyl ditosylate 9 and the enantiomers of di-tert-butyl-substituted tetraethylene glycol (R,R)-8 and (S,S)-8 in the presence of a strong base. One of them, (R,R)-7, was covalently attached to silica gel, and this chiral stationary phase (CSP) separated four selected racemic organic ammonium perchlorates into their enantiomers by column chromatography.     

Muricatetrocins A and B and Gigantetrocin B: Three New Cytotoxic Monotetrahydrofuran-Ring Acetogenins from Annona muricata

Extracts from the seeds of Annona muricata yielded three new Annonaceous acetogenins: muricatetrocin A (= (5S)-3-{(2R)-2-hydroxy-9-{(2R,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 1 ), muricatetrocin B (= (5S)-{(2R)-2-hydroxy-9-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxyheptadecyl]furan-2-yl}nonyl}-5-methylfuran-2(5H)-one; 2 ), and gigantetrocin B (= (5S)-3-{(2R)-2-hydroxy-7-{(2S,5S)-tetrahydro-5-[(1S,4R,5R)-1,4,5-trihydroxynonadecyl]furan-2-yl}heptyl}-5-methyl-furan-2(5H)-one; 3 ). Their C-skeletons were deduced by mass spectrometry. Configurations were determined by ¹H-NMR of ketal derivatives and 2D-NMR experiments utilizing Mosher esters. A previously described compound, gigantetrocin A (= (5S)-3-{(2R)-2-hydroxy-7-{(2S,5S)-tetrahydro-5-[(1S,4S,5S)-1,4,5-trihydroxynonadecyl]furan-2-yl}heptyl}-5-methylfuran-2-(5H)one; 4 ), was also isolated and is new to this species. Compounds 1–4 were all selectively cytotoxic for the HT-29 human colon-tumor cell line with potencies at least 10 times that of adriamycin.     

Molecular recognition as shown by the solvent extraction of (R)- and (S)-[α-(1-naphthyl)ethyl] ammonium picrate or orange 2 by chiral pyridino-crown ethers

A solvent extraction technique was used to determine equilibrium constants for the reactions occurring when an aqueous phase containing [-(1-naphthyl)ethyl]ammonium ions [(R)- and (S-isomers] is equilibrated with a chloroform phase containing chiral substituted pyridino-18-crown-6 ligands. Selectivity coefficients and equilibrium constants for the interactions in chloroform solutions were calculated. The existence of two different types of ion pairs separated by the macrocycle molecule was detected from the UV spectra. One ion pair has a nearly complete separation of the picrate anion from the protonated amine by the ligand. The other has the picrate ion only partly separated from the cation by the macrocycle.     

Assembling Quasi‐enantiomeric Octahedral Complexes of Different Metals via Quasi‐racemate Crystallization

Aiming at a general methodology for binary co‐assembly of complexes of different metals through quasiracemate crystallization, the hexadentate ligand 1 comprised of the chiral bipyrrolidine core and two bipyridine peripheral arms is introduced. Ligand 1 was found to bind in a fully diastereoselective and uniform mode around Zn^II, Fe^II and Cd^II giving coordinatively inert octahedral “chiral‐at‐metal” complexes with the Δ₄Λ₂/Λ₄Δ₂ wrapping mode. Equimolar mixtures of quasienantiomeric pairs of these complexes exhibited a clear tendency to pack as quasiracemates as was revealed from the crystallographic structures of [(R,R)‐ 1 ‐Zn](PF₆)₂/[(S,S)‐ 1 ‐Fe](PF₆)₂ and [(R,R)‐ 1 ‐Zn](PF₆)₂/[(S,S)‐ 1 ‐Cd](PF₆)₂, in an isomorphous fashion to that of the racemic compound [rac‐ 1 ‐Zn](PF₆)₂ in space group C2/c.     

Synthesis and Complexation Properties of Pyrimidine-Derived Crown Ether Ligands

Five new proton-ionizable macrocyclic ligands containing a pyrimidone-subcyclic unit, 6–10 , were prepared from the previously prepared pyrimidinocrown ethers 1–5 (see Figure 1 and Scheme 1). One of the new proton-ionizable crown ethers is chiral. The proton-ionizable pyrimidonocrown ethers were prepared in high yields by treating the appropriate methoxy-substituted pyrimidinocrown with 5 M sodium hydroxide in a 50% alcohol-water mixture. Complexation properties of four of the pyrimidine-derived macrocycles were studied by various nmr techniques. Pyrimidono-18-crown-6 (9) forms a strong complex with benzylammonium perchlorate and also forms a complex with benzylamine. (S, S)-Dimethyl-substituted pyrimidino- and pyrimidono-18-crown-6 ligands 4 and 9 form stronger complexes with the (R)-form of α-(1-naphthyl)ethylammonium perchlorate than with the (S)-form. (S, S)-Dimethyl-substituted pyrimidono-18-crown-6 ( 9 ) also forms a stronger complex with (R)-α-(1-naphthyl)ethylamine than with the (S)-form. The crystal structure for compound 7 is reported.