Natural Abundance 13C-NMR. of Reduced Isoalloxazine

When an isoalloxazine derivative ( 1 ) was reduced ( 2 ) its ¹³C-NMR. resonances were all shifted upfield and the largest shifts were observed for C (4a), C(6) and C(8) but downfield shifts for C(2), C(4) and C(10a). The results and their biochemical implications are shortly discussed.     

Structure elucidation,complete NMR assignment and PM5 theoretical studies of new hydroxy‐aminoalkyl‐α,β‐unsaturated derivatives of the macrolide antibiotic josamycin

Four new hydroxy‐aminoalkyl derivatives of α,β‐unsaturated macrolide‐josamycin (2–5) have been synthesised and their structures have been studied by means of ¹H and ¹³C NMR and FT‐IR methods. Complete assignment of resonances in the ¹H and ¹³C NMR spectra has been made on the basis of ¹H? ¹³C HSQC, ¹H? ¹³C HMBC, ¹H? ¹H COSY, ¹H? ¹H NOESY 2D experiments. Spectroscopic data indicated that for the derivatives 3 and 4 some equilibrium between two different structures exists in contrast to derivatives 2 and 5. The lowest‐energy structures of the new derivatives of josamycin have been calculated and visualised by PM5 method at semi‐empirical level of theory, taking into account the NMR and FT‐IR data. The most significant differences between the structures of josamycin and its newly synthesised derivatives' were found in the conformation of the macrolide aglycone part and in the mutual orientation of the 4‐O‐isovalerylmycarosylmycaminose moiety relative to the aglycone part. PM5 semi‐empirical calculations indicated that the structures of the new macrolide derivatives are stabilised by rather weak intramolecular hydrogen bonds in agreement with spectroscopic data. Antimicrobial properties of the new derivatives 2–5 as well as those having an acetate group at C‐3 (6 and 7) were determined and compared to that of the parent macrolide antibiotic josamycin (1). Copyright © 2010 John Wiley & Sons, Ltd.     

13C- and 1H-NMR. Spectra of ortho-benzoquinones. On the assignment problem in 13C spectra

¹³C- and ¹H-NMR. spectra of ortho-benzoquinone 1 and its methyl derivatives have been analysed. By means of heteronuclear double resonance experiments it is shown that assignments given in the literature for the olefinic carbon resonances of 1 and of a series of substituted ortho-benzoquinones have to be inverted. ¹³C-carbonyl frequencies of various six-membered cyclic ketones are presented.     

1H and 13C NMR study of dihydro derivatives of methylphenobarbital

Sodium borohydride reduction of methylphenobarbital leads to the formation of two different dihydroderivatives, reduced either in position 4 or position 6. The structures of the derivatives have been determined through analysis of the ¹H and ¹³C NMR spectra of phenobarbital, methylphenobarbital and their derivatives. Detailed interpretation of the spectra and the resulting spectral parameters indicate conformations where the hydroxyl groups are axial and trans to the ethyl group. In these configurations the phenyl ring becomes equatorial. The results also allow an unambiguous assignment of the resonances of the phenyl carbons 2′(6′) and 3′(5′) of phenobarbital and the carbonyl carbons 4 and 6 of methylphenobarbital, differing interpretations having been previously advanced in the literature.     

Natural abundance 13C NMR investigation of substituted bromobenzene using noise decoupling of proton resonances

The natural abundance ¹³C NMR spectra of bromobenzene and ten derivatives have been obtained using the technique of noise modulated decoupling of the proton resonances. Assignments have been made for all ¹³C resonance signals using an additivity rule. The chemical shifts of the aromatic carbon nuclei in the para-substituted compounds are discussed in terms of the Taft parameters (σ_R, σ_I) and the electronegativity of the substituent.     

A Comparative 13C-NMR. Study on Various Reduced Flavins

Various two-electron reduced flavin derivatives have been investigated by natural abundance ¹³C-NMR. spectroscopy. Some selectively ¹³C-enriched compounds were synthesized to ensure the assignment of some of the quaternary C-atoms of the flavin molecule. Addition of two electrons to oxidized flavin leads to upfield shifts of all resonances except for those due to C(5a), C(9) and C(10′α). The largest upfield shift is observed for C(4a). Also some direct and two-bond coupling constants are reported. Theoretical calculations by INDO show that a rather good correlation exists between the calculated π-electron densities and the observed chemical shifts of the two-electron reduced molecule. For the oxidized molecule, the correlation is less satisfactory. Most substitution effects are additive, but some deviations in some compounds are observed indicating structural differences between the compounds in question. The chemical shifts are also discussed in terms of the chemical reactivity of the oxidized and reduced flavin molecule.     

Carbon-13 NMR spectra of rifamycins

The natural abundance ¹³C Fourier transform magnetic resonance spectra of rifamycin S and some of its derivatives have been studied. A combination of five different approaches has made unambiguous assignments for most of the resonances possible: (1) comparative study of the non- decoupled and noise-decoupled spectra; (2) ¹³C spectral characteristics; (3) spectral comparison between derivatives; (4) selective proton decoupling; (5) biogenetic evidence. Pulse and Fourier transform ¹³C NMR spectroscopy provides a more complete picture of these complex molecules than was previously obtained by ¹H NMR spectroscopy.     

13C n.m.r. spectroscopy: Comparison of the spectra of some dimeric Catharanthus alkaloids and their derivatives

The ¹³C n.m.r. spectra of some dimeric Catharanthus alkaloids are reported and assigned. Methods devised to aid in the assignment of resonances in complex molecules are described. The ¹³C n.m.r. spectra of several derivatives of vinblastine are discussed.     

Carbon-13 NMR spectra of fusicoccin and its derivatives

The ¹³C NMR spectra of fusicoccin, some of its cometabolites and derivatives were studied. Using standard Fourier transform techniques, T₁ relaxation time measurements and lanthanide shift reagents, the resonances of individual carbon-13 nuclei were assigned.     

A carbon-13 study of relaxation in the mesophases of 5O·7 and the 5CB homologous series

Abstract

Carbon-13 spin-lattice relaxation times of the protonated ring carbons have been measured at 22·6 MHz in the nematic and all four smectic phases of 5O·7 (4-n-pentyloxybenzylidene-4′-n-heptylaniline). Dong has obtained the deuterium spectral densities J ₁ and J ₂ at 15·4MHz for the deuterated aniline ring of 5O·7-d ₄, and has presented and applied a theory in which the spectral densities are expressed in terms of the diffusion constants D∥ and D?. His results are used to calculate ¹³C relaxation times from the spectral densities J ₀, J ₁ and J ₂. The calculated ¹³C spin-lattice relaxation times are then compared with our experimental values to test the theory. The ¹³C spin-lattice relaxation times of all the resolved resonances in the various phases of the first four members of the 5CB homologous series have been published previously. Dong has also published an analysis of 5CB deuterium data, and we use his results for the diffusion constants D∥ and D? to calculate ¹³C relaxation times of the protonated aromatic carbons of 5CB, 6CB, 7CB and 8CB. The ¹³C relaxation times of the unprotonated aromatic carbons of the 5CB series are calculated in the manner of Wittebort et al., but using the spectral density expressions developed by Dong. The calculated ¹³C spin-lattice relaxation times of the 5CB homologous series are then compared with our experimental values to test the theory for the protonated and unprotonated ring carbons.     

Nucleotides. Part LXXVI

A series of new fluorescing 8‐(6‐hydroxyhexyl)isoalloxazine (=8‐(6‐hydroxyhexyl)benzo[g]pteridine‐2,4(1H,3H)‐dione) derivatives 4 – 13 were synthesized from 6‐[(6‐hydroxyhexyl)amino]uracil ( 2 ) with 1‐chloro‐4‐nitrosobenzene via 8‐chloro‐10‐(6‐hydroxyhexyl)isoalloxazine ( 3 ) and subsequent substitution of the Cl‐atom of 3 by various amines (Scheme). Analogously, 8‐substituted 10‐{3‐[(2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)methoxy]propyl}isoalloxazines 19, 20 , and 23 – 25 were prepared which yielded on deprotection the corresponding 10‐[3‐(2,3‐dihydroxypropoxy)propyl]alloxazines 21, 22 , and 26 – 28 . Their conversion into the 3″‐O‐(4,4′‐dimethoxytrityl) derivatives 29 – 33 and subsequent transformation into the corresponding 2″‐(2‐cyanoethyl N,N‐diisopropylphosphoramidites) 34 – 38 led to new building blocks for oligonucleotide synthesis. A series of 21‐mer oligodeoxyribonucleotides carrying the fluorescing isoalloxazine 37 in various positions of the chain were assembled in a DNA synthesizer. Combination with the complementary sequence yielded the stable duplexes 40 – 54 showing by the melting temperatures T_m that the fluorophor ( F ) does not harm the stability of the unmodified duplex 39 (Table).     

Carbon-13 NMR study of isoxazolopyridine systems

The ¹³C NMR spectra of all azabenzenoid isoxazolopyridines and some of their chloro derivatives are discussed. All ¹³C resonances were unambiguously assigned by means of gated decoupled spectra, from which one-bond and long-range ¹³C? ¹H coupling constants have been determined from line splittings.     

Absorption and Fluorescence Studies on Neutral and Cationic Isoalloxazines

The electronic properties of a variety of methylated isoalloxazine derivatives have been investigated with absorption and fluorescece techniques (Table 1). The spectral effects of methyl substitution at different positions in the isoalloxazine ring are interpreted in terms of different bond orders between the C-atoms of the methyl groups and of the aromatic ring. Methyl groups at C(6) or C(9) induce quenching of the fluorescence and shortening of the lifetime whereas a methyl group at C(7) has an opposite effect. The quenching effect might be due to strain in the molecular framework caused by the methyl groups. The lowest energy levels of the isoalloxazine cations are shifted to higher energy as compared to the neutral isoalloxazines. Apart from these shifts the trends in spectral behaviour upon methylation are similar to those observed for the neutral isoalloxazine (cf. Table 2). The fluorescence of the isoalloxazine cations is strongly quenched in auqeous solution and their lifetime much shortened. These observations indicated that there is substantial interaction between the charged fluorophore and the water dipoles and that this interaction produces efficient radiationless deactivation of the first excited singlet state.     

1H and 13C chemical shifts for acridines: Part XVIII. 9‐Chloroacridine and 9‐(N‐allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives

The¹H and ¹³C NMR resonances for acridine derivatives 9‐substituted with chloro, allylamino and propargylamino groups were completely assigned using a concerted application of gs‐COSY, gs‐HMQC and gs‐HMBC experiments. 9‐(N‐Allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives present amino–imino tautomerism including a large broadening of ¹H and ¹³C NMR signals at room temperature. To obtain suitable resolution, therefore, these latter compounds were studied at 370 K in DMSO‐d6 solutions and showed a complete shift towards the imino tautomers. Copyright © 2003 John Wiley & Sons, Ltd.     

A regioselective route to 3-alkyl-1-aryl-1H-pyrazole-5-carboxylates: Synthetic studies and structural assignments

Ethyl 2,4-dioxooctanoate ( 1 ) was selectively protected as the 2-(methoxyimino) derivative 2 . When 2 was reacted with phenylhydrazine hydrochloride, ethyl 3-butyl-1-phenyl-1H-pyrazole-5-carboxylate ( 4 ) was favored over the corresponding 5-butyl-1-phenyl-1H-pyrazole-3-carboxylate product 5 by a ratio of at least 6:1, a complete reversal of the regioselectivity observed for 1 . The structures of 4 and 5 were assigned definitively by NOE difference experiments. Regiochemical and configurational assignments of the mono- and bis(methoxyimino) derivatives of 1 were also achieved by ID and 2D ¹H and ¹³C nmr methods.     

Assignment of the 5,6-Double-Bond Configuration in Iloprost and Isoiloprost from 13C-NMR Shifts Determined by 2D Methods

The configurations of the 5,6-double bond in the carbacyclins iloprost ( 3 ; (E)) and isoiloprost ( 4 ; (Z)) are based on a complete assignment of the ¹³C and ¹H resonances determined by 1D and 2D ¹³C-NMR and ¹H-NMR methods.     

FTIR and carbon-13 NMR spectra of chalcocarbonyl(5,10,15, 20-tetraphenylporphinato)iron(II) complexes

The room-temperature, FTIR difference spectra of the solid chalcocarbonyl(5,20,15,20-tetraphenylporphinato)iron(II) derivatives, FeTPP(CX) and FeTPP(CX)L (X = S, Se; L = pyridine, EtOH), have been recorded (in CsI disks) in order to examine the influence of the axially bound CX and L ligands on the vibrations of the metal-porphyrin ring. The ¹³C NMR spectra of these complexes in CD₂Cl₂ have been measured at room temperature for a similar reason. The vibrations and ¹³C resonances of the metal-porphyrin ring are only slightly affected by the presence of the axial ligands. The positions of the ¹³CX NMR resonances and the ν(CX) modes in the i.r. are dependent on the nature of L.     

Synthesis and stereochemical assignment of 7-arylidene and 7-heteroarylidene morphinan-6-ones

A number of (E)-7-arylidenenaltrexones were synthesized by azeotropic distillation of water from a benzene solution of naltrexone and an aromatic aldehyde (benzaldehyde, 4-chloro- and 4-fluorobenzaldehyde, 3-and 4-pyridinecarboxaldehyde and 1-methyl-2-imidazolecarboxaldehyde) using piperidine as a catalyst. In addition, (E)-7-benzylidenenaloxone was prepared by the previously published Claisen-Schmidt condensation using sodium hydroxide in methanol. The stereochemistry of these arylidene derivatives 3–9 was determined to be (E) by means of nuclear Overhauser enhancement experiments. The ¹³C nmr spectra of (E)- 3–9 are recorded in deuteriochloroform and those of the hydrochlorides in deuteriodimethyl sulfoxide.     

Synthesis,structural and conformational study of selected <Emphasis Type="Italic">N</Emphasis>-substituted phthalimides

This paper synthesizes N-substituted phthalimides derived from nitrogen heterocycles as potential 5-HT₄ ligands by using the Mitsunobu reaction. Conformational studies of some of the new compounds have been conducted using ¹H and ¹³C-NMR spectroscopy. Proton and carbon resonances were achieved through the application of one-dimensional selective NOE, two-dimensional NMR techniques-homonuclear COSY-45, NOESY and heteronuclear ¹H-¹³C HMQC correlated spectroscopy- and double resonance experiments. The crystal structure of compound 1 was determined by X-ray diffraction.