Syntheses and properties of chiral pentahomothiazacalix[3]arenes

Chiral calixarene analogs incorporating an aminoethanethiol unit such as L-cysteine into their rings were prepared. Conformational analysis of the macrocycles by using ¹H and ¹³C nmr spectroscopy revealed that their preferred conformation was a cone, which was more stable in chloroform than in toluene. The introduction of an aminoethanethiol moiety into the macrocyclic ring caused ring fluctuation, however, the carboxylic acid derivative was a highly rigid structure in the cone form. The ¹H nmr and circular dichroism spectra of the macrocycles showed the existence of chirality of the phenol-formaldehyde unit, which was induced by the chirality of the cysteine moiety.     

Synthesis and properties of bowl‐shaped homotriazacalix[3 and 6] arenes and the acyclic analogues

Bowl‐shaped chiral homotriazacalixarenes were prepared by the cyclization reactions of chiral triamines with three equimolar amounts of bis(chloromethyl) phenols or bis(chloromethyl) phenol‐formaldehyde dimers in moderate yields. The corresponding acyclic phenol‐formaldehyde oligomers were also synthesized. The structural analysis of the macrocycles by nmr and circular dichroism spectra imply the existence of chiral transmission from the point chirality of the cysteine bridge to the cyclophane moiety. Their cyclic and acyclic compounds have a π‐base cavity large enough to include the ammonium ion.     

Syntheses of chiral homoazacalix[4]arenes incorporating amino acid residues: molecular recognition for racemic quaternary ammonium ions

Chiral calixarene analogues incorporating amino acid residues into the macrocyclic rings were prepared from the cyclization reactions of bis(chloromethyl)phenol-formaldehyde tetramer with amino acid methyl ester in moderate yields. The macrocycles form a chiral concavity, which is induced by the chiral transmission from the point chirality of the amino acid residues to the phenol-formaldehyde tetramer unit. The macrocycles have the cavity pi-basic enough to include the quaternary ammonium ion due to the cation-pi interaction and can serve as a shift reagent for racemic ammonium ions during 1H NMR analysis.     

Über chirale Methylzinkaminoalkoxide

Chiral Methylzinc Amino Alkoxides Dimethylzinc reacts with (S)‐N‐methylpyrrolidinyl‐2‐methanol, (R/S)‐1‐phenyl‐2‐(N‐methylamino)‐ethanol, and (S)‐α,α‐diphenyl‐2‐pyrrolidinyl‐2‐methanol in molar ratio 1 : 1 with formation of the corresponding methylzinc amino alkoxides 1 – 3 . As a consequence of the Zn–N‐interaction new centres of chirality containing asymmetric surrounded N‐atoms are formed. Compounds 1 – 3 were characterized by their ¹H and ¹³C nmr spectra. The crystal structures of 1 – 3 were determined by single crystal structur analysis. 1 and 2 are trimeric in solid state, 3 is forming dimeric molecules.     

Utilization of deuterium labelling and 13C NMR spectroscopy in the investigation of the condensation of 1-Methyl-5-nitroimidazole-2-aldehyde and 2-Amino-4-methylpyrimidine

The product obtained condensing l-methyl-5-nitroimidazole-2-aldehyde with 2-amino-4-trideuteriomethyl-pyrimidine and showing total deuterium incorporation at one of the olefinic carbons and partial deuterium incorporation para to the amino group, served to assign ¹³C and ¹H resonances in the condensation products 3. The nature of the species undergoing condensation has been inferred from labelling experiments and from ¹H and ¹³C nmr spectra of precursors and products in dimethylsulfoxide and trifluoroacetic acid.     

Synthesis and NMR studies of thiazolidine-4-carboxylic acid derivatives containing a nitro ester function

The preparation of thiazolidine-4-carboxylic acid derivatives containing a 2-nitrooxyethylamine group, potentially active as vasodilators, is reported. Their ¹H nmr studies carried out to establish the configuration of the C2 stereocenter and the full assignment of their ¹H and ¹³C nmr spectra, are also reported.     

The Role of Amino Acid Esters and the Amide Group in the Chiral Induction Process by a Novel Monoamide‐Linked Monozinc Bisporphyrinate

A monoamide‐linked monozinc bisporphyrinate for monodentate chiral guests was designed and synthesized. It was used as a host to complex with amino acid esters; the resulting CD spectra showed typical bisignate shape, which suggest the ability to transfer chirality from amino acid esters. The molecular structure of the host indicates that amino acid esters function as monodentate ligands in the host‐guest complex. ¹H NMR spectroscopic studies suggest formation of a hydrogen bond between the amide NH and the carbonyl oxygen groups of the amino acid ester. The possible mechanism of the chiral induction process was further studied by DFT calculations.     

甾体磷酰胺类缀合物在电喷雾质谱中的裂解特征

Novel steroidal phosphoramidate conjugates of 3'-azido-2',3'-dideoxythymidine(AZT)and amino acid esterswere synthesized and determined by positive and negative ion electrospray ionization mass spectrometry.The MSfragmentation behaviors of the steroidal phosphoramidate conjugates have been investigated in conjunction withtandem mass spectrometry of ESI-MS/MS.There were three characteristic fragment ions in the positive ion ESImass spectra,which were the Na adduct ions with loss of steroidal moiety,amino acid ester moiety from pseudomolecular ion(M Na)~ ,and the phosphoamino acid methyl ester Na adduct ion by α-cleavage of the phosphora-midate respectively.The main fragment ions in negative ion ESI mass spectra were the ion(M-HN_3)~-,the ion(M-AZT-H)~-,and the ion(M-steroidal moiety-H)~- besides the pseudo molecular ion(M-H)~-.Thefragmentation patterns did not depend on the attached amino acid ester moiety.     

The first synthesis of thieno[c]isoquinolines and an improved synthesis of phenanthridine and thieno[c]quinolines through pd(0) catalyzed coupling of ortho-formylarylboronic acids with functionalized aryl halides

All three isomeric hitherto unknown thieno[c]isoquinolines have been synthesized in high yields by the Pd(0)-catalyzed coupling of 2-formylbenzeneboronic acid with t-butyl-N-(ortho-halothienyl)carbaniates. When 2-bromoacetanilide, instead of 2-bromoaniline, was coupled with orth-formylarylboronic acids under Pd-catalysis, phenanthridine and thieno[c]quinolines were obtained in improved yields. Total assignments of ¹H nmr spectra of thieno[c]isoquinolines and thieno[c]quinolines are reported. Assignments are based on high resolution 300 MHz ¹H nmr spectra, two-dimentional ¹H-¹³C chemical shift correlation spectra and one-dimentional INADEQUATE ¹³C nmr spectroscopy.     

Unusual schmidt rearrangement of 7,7a,8,9,10,12-hexahydro benzo[h]pyrrolo[1,2-b]-isoquinoline-7,10-dione

The reaction of 7,7a,8,9,10,12-hexahydrobenzo[h]pyrrolo [1,2-b]isoquinoline-7,10-dione 2 with sodium azide in sulfuric acid afforded the unexpected cyano derivative 5 . The proposed structure for 5 is supported by ¹³C nmr, ¹H nmr and HMBC spectra.     

Mannich reaction on 2-(2-benzofuranyl)-1H-indole. Determination of structure by NMR spectroscopic techniques

Analysis of the product from the Mannich reaction of 2-(2-benzofuranyl)-1H-indole via ¹H and ¹³C nmr spectroscopy was performed. The studies included use of Pr(Fod)₃ shift reagent, proton-coupled ¹³C spectra, deuterium isotope induced shifts and protonation studies. It was found that the reaction occurred on the indole moiety at C-3.     

Carbon-13 and proton magnetic resonance spectra of 2,4-disubstituted 3,3-diphenyltetrahydrofurans derived from isomethadone and isomethadol

Proton and carbon-13 nmr spectra for cis- and trans-2-ethyl-3,3-diphenyl-4-methyltetrahydrofurans and 2-ethylidene-3,3-diphenyl-4-methyltetrahydrofuran, derived from the pyrolysis of the quaternary ammonium salts of the diastereomeric isomethadols and isomethadone, respectively, are reported. ¹H and ¹³C chemical shifts and ¹H-¹H coupling constants have been assigned in each case. The isomeric teterahydrofurans have been analyzed in terms of a half-chair conformation, and an envelope conformation for the ethylidene derivative.     

Cryptolepinone vs. Hydroxycryptolepine: Resolution of a question of substituent functionality and double bond isomerization

An indolo[3,2-b]quinoline alkaloid bearing an N-methyl substituent at N5, and an oxygen moiety at the 11-position has been variously described as both cryptolepinone and 11-hydroxycryptolepine by independent research groups. The structure of this alkaloid is unequivocally confirmed as the former, cryptolepinone, with substantial changes in double bond isomerization relative to that which would be required if it were indeed the latter. The structure of the alkaloid was confirmed by, total assignment of the ¹H, ¹³C, and ¹⁵N nmr spectra at natural abundance using 3 mm micro inverse nmr probe technology at 400 and 500 MHz.     

New one step synthesis of crown compounds containing a 1,3,4‐thiadiazole moiety

New macrocyclic polyether compounds containing a 2,5‐bis(2‐hydroxyphenyl)‐1,3,4‐thiadiazole moiety have been prepared by a nucleophilic substitution reaction involving ethylene or polyethylene glycol ditosylate and a bisphenol, the 2,5‐bis(2‐hydroxyphenyl)‐1,3,4‐thiadiazole, with solid anhydrous carbonate as a base. The structures of the macrocycles obtained were firmly established by ¹H and ¹³C nmr spectroscopy and their mass spectra.     

Preparation and characterization of 16-benzoylated tetraaza[14]annulenes

The condensation reaction between tetraaza[14]annulene ( 1 ) and a series of para-substituted benzoyl chlorides led to the 16-benzoylated corresponding products in 13–21% yields, but 1 was unreactive with alkyl acid chlorides and easily cleaved in macrocyclic framework. The mass spectra show the presence of molecular ion peaks which support the 16-benzoylated products. A strong ir band due to the C = N stretching mode of the macrocyclic moiety was observed at 1610 cm^?1 and shifted slightly toward higher energy upon benzoylation. An intense ir band which was associated with a C = 0 stretching mode was newly observed at 1640 cm¹. The very strong absorption band about 29000 cm^?1 was attributed to the π ? π* transition and gave a slight shift to higher frequency on benzoylation. All proton signals except for methyl protons exhibit downfield shifts due to the deshielding effect of the substituted benzene ring, but the methyl proton peaks show upfield shifts due to the shielding effect caused by the magnetic anisotropy of the substituted benzene ring. The ¹³C nmr result is also in accord with that of ¹H nmr.     

Stereospecific control of peptide gas‐phase ion chemistry with cis and trans cyclo ornithine residues

We report non‐chiral amino acid residues cis‐ and trans‐1,4‐diaminocyclohexane‐1‐carboxylic acid (cyclo‐ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen‐rich cation radicals produced by electron‐transfer dissociation. Upon collision‐induced dissociation (CID) in the slow heating regime, peptide cations containing trans‐cO residues undergo facile backbone cleavages of amide bonds C‐terminal to trans‐cO. By contrast, peptides with cis‐cO residues undergo dissociations at several amide bonds along the peptide ion backbone. Diastereoisomeric cO‐containing peptides thus provide remarkably distinct tandem mass spectra. The stereospecific effect in CID of the trans‐cO residue is explained by syn‐facially directed proton transfer from the 4‐ammonium group at cO to the C‐terminal amide followed by neighboring group participation in the cleavage of the CO―NH bond, analogous to the aspartic acid and ornithine effects. Backbone dissociations of diastereoisomeric cO‐containing peptide ions generate distinct [b_n]⁺‐type fragment ions that were characterized by CID‐MS³ spectra. Stereospecific control is also reported for electron‐transfer dissociation of cis‐ and trans‐cO containing doubly charged peptide ions. The stereospecific effect upon electron transfer is related to the different conformations of doubly charged peptide ions that affect the electron attachment sites and ensuing N―C_α bond dissociations.     

Complete assignment of the 1H and 13C NMR Spectra of 11,12-Dimethoxy[1]benzothieno[3,2-a]-4,7-phenanthroline and its 8-Chloro Analogue: Concerted Use of Two-Dimensional NMR Techniques

The ¹H and ¹³C nmr spectra of 11,12-dimethoxy[1]benzothieno[3,2-a]-4,7-phenanthroline and its 8-chloro precursor were totally assigned using a combination of two-dimensional nmr techniques. After correlation of the majority of the proton signals by a COSY spectrum and one-bond heteronuclear correlation, the full assignment of the ¹H and ¹³C nmr spectra of the novel heterocyclic compounds required the application of long-range CH coupling information particularly for quaternary carbon resonance assignments and the orientations of individual spin systems relative to one another. Key long-range heteronuclear couplings in both compounds served to confirm the one-bond heteronuclear correlations. Unequivocal interpretation of the spectral data leads to the complete assignments of the resonances.     

Autocorrelated 13c-13c double quantum coherence two-dimensional nmr spectroscopy: Utilization of a modified version of the technique as an adjunct in the total assignment of the 1h- and 13c-nmr spectra of the mutagen phenanthro[3,4-b]thiophene

Development of successively higher field nmr spectrometers has facilitated the study of increasingly more complex molecules, although smaller molecules such as phenanthro[3,4-b]thiophene still offer very substantial assignment problems because of the highly congested nature of their ¹H- and ¹³C-nmr spectra. Assignments of such spectra, if they are to be unequivocal, frequently require the utilization of two-dimensional nmr spectroscopic techniques. Total assignments of the ¹H- and ¹³C-nmr spectra of phenanthro[3,4-b]thiophene are reported. Assignments were based on a conventional high resolution 500 MHz ¹H-nmr spectrum, autocorrelated two-dimensional ¹H-nmr spectra (COSY), two-dimensional ¹H-¹³C chemical shift correlation spectra and a modified version of autocorrelated ¹³C-¹³C double quantum coherence two-dimensional nmr spectroscopy. From NOE measurements, a separation of 1.99 Å between H1 and H11 was computed, suggesting that phenanthro[3,4-b]thiophene has a pronounced helical conformation in solution.     

Conformational analysis of benzoannulated nine-membered rings. Part 3. 1,4,5,7-Tetrahydro-3H-2,6-benzodiselenine and its 4-spiro derivatives

The ¹H and ¹³C nmr spectra of 1,4,5,7-tetrahydro-3H-2,6-benzodiselenine (1) and three 4-spiro derivatives 2–4 as well as the ⁷⁷Se nmr spectra of 2 have been recorded at different temperatures in order to investigate their conformational behavior. It was found that in analogy to corresponding dithionins the molecules adopt a chiral ground state conformation (Figure 2), and coalescence effects are due to racemization.     

Recognition by a new chiral dimethyl-substituted phenanthrolino-18-crown-6 diester ligand of the enantiomers of various organic ammonium perchlorates

Two new chiral dimethyl-substituted phenanthrolino-18-crown-6 diester ligands [(S,S)- 3 ] and [(S,S)- 4 ] (see Figure 1) were prepared through the reactions of 1, 10-phenanthroline-2,9-dicarboxylyl dichloride with (S,S)-dimethyl-substituted tricthylene glycol and (S,S)-dimethyl-substituted benzotricthylene glycol, respectively. The complexation of (S,S)- 3 with the enantiomers of various organic ammonium perchlorates in various solvent systems was studied by ¹H nmr spectral techniques and molecular mechanics. The degree of enantiomeric recognition was determined by the difference in the free energy of activation values (ΔΔG^?_C) and the difference in log K values for these interactions. The extensive π system in the ligand plays an important role for the strong interaction and recognition. The ¹H nmr NOESY spectra and molecular mechanics calculations for the interactions of the new ligand with the organic ammonium salts further proved the existence of a π-π interaction.