The Configuration of Naturally Occurring Iridoid Glucosides at C(6) and C(8): A Complementary Assignment Aid by 13C-NMR. Spectroscopy

Evidence is presented which demonstrates that ¹³C-NMR. spectroscopy can be used with confidence in evaluating the configuration of R¹R²CHOH centers at C(6) and C(8) of iridoid glucosides.     

13C-NMR-spektren stereoisomerer 1,4-dialkylspiro[4.5]decan-derivate

The ¹³C NMR spectra of a series of 7-substituted 1,4-dialkylspiro[4.5]decanes and of suitable reference compounds are assigned and the derived substituent effects upon the chemical shifts are discussed. In particular, consideration of γ and δ-effects allows the differentiation between 1,4-cis- and 1,4-trans-compounds. Furthermore, the (relative) configuration of the chiral spiroatom C-5 is determined.     

The assignment of the 1H and the 13C NMR chemical shifts of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam

The assignment of the signals in the ¹³C and ¹H NMR spectra of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam is difficult for the signal pairs C-2 and C-4, C-1 and C-3, (C-1)? H, (C-2)? CH₃ and (C-4)? CH₃. The ¹³C NMR spectrum recorded under gated decoupling conditions provide long-range couplings which make possible an unambiguous assignment of the ¹³C NMR signal pairs. Application of the ¹H CW off-resonance decoupling technique in recording the ¹³C NMR spectra enables the assignment information from the ¹³C NMR spectrum to be transferred to the ¹H NMR spectrum.     

Structural revision of ajugol and myoporoside

An analysis of existing ¹³C NMR data shows that the structures reported for the iridoid glucosides ajugol and myoporoside should be interchanged. Consequently, the structures of ajugoside and laterioside, both acyl-derivatives of ajugol, as well as that of 8-O-acetyl-myoporoside need revision.     

The stereochemistry of 2,4-disubstituted γ-butyrolactones and 2,4,6-trisubstituted-5,6-dihydro-4H-1, 3-oxazines

2,4-Disubstituted butyrolactones and 2,4,6-trisubstituted-5,6 dihydro-4H-1,3-oxazines show similar features in their ¹H and ¹³C- NMR spectra. Two geminal ring hydrogens of cis isomers give rise to a complex ABXY spectra when the substituent is alkyl or aryl. In spectra of trans isomers these patterns are degenerated. When R is OMe(in 4) or OCOMe (in 6) the difference in chemical shifts of geminal protons and vicinal coupling constants cannot be used for diagnosis. In ¹³C spectra ring carbons C-2 and C-3 in lactones and C-4 and C-5 in oxazine of trans isomers show a small but consistent shift to higher fields.     

Carbon-13 NMR studies of flavonoids—III: Naturally occurring flavonoid glycosides and their acylated derivatives

¹³C NMR spectra for a variety of flavonoid glycosidcs are presented and analysed. Evidence is presented which demonstrates that ¹³C NMR spectroscopy is a valuable technique for distinguishing the sites of methylation, glycosylation and acylation in flavonoid glycoiides, and in some cases the nature and sites of specific sugars and acyl groups. Shifts observed in the spectrum on derivization of the 5-OH group are unusual. The ring size and C-1 configuration in glycosidic sugars are also evident from the spectra. Structural assignments are made for several glycoides.     

Assignment of Anomeric Configuration and Identification of Carbohydrate Residues by 13C NMR: Arabino- and Ribopyranosides and Furancsides

Abstract

A ¹³C NMR fingerprint method previously developed for galactosides and glucosides is extended to arabinosides and ribosides. This approach demonstrates the capability of ¹³C NMR to determine ring size and anomeric configuration in four isomeric arabinosides and ribosides.     

Stereochemical studies of substituted 6,7- benzomorphan derivatives by 13C and 1H NMR spectroscopy

The ¹³C NMR spectra of a series of 6,7-benzomorphan derivatives variously substituted at C-5 and C-9 by methyl and at C-3 by cyano, alkyl and aralkyl groups, together with certain 3-cyano, 3-allyl or benzyl congeners, are reported and chemical shift data analysed in terms of the configuration of isomeric pairs and compounds isolated as single diastereoisomers. Special attention is given to the consequences of γ-shielding interactions, the effects of the nitrogen lone-pair orbital and anisotropic shielding by the aromatic region of the molecule. Deductions of stereochemistry are supported by ¹H NMR data and the NMR features of the corresponding methiodide salts.     

Assigning the C-15 configuration of 15-hydroxy-, 15-methoxy-, 15-ethoxy-hexahydrofurofuran neoclerodane diterpenoids

Examination of ¹H and ¹³C NMR spectra allows the establishment of rules for assigning the correct configuration at C-15 of 15-hydroxy-, 15-methoxy-, 15-ethoxy-hexahydrofurofuran neoclerodane diterpenoids. The structure of several diterpenoids has been assigned or ammended.     

Chloroscabrolides, chlorinated norcembranoids from the Indonesian soft coral Sinularia sp.

Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded two known and three new C-4 norcembranoids, named chloroscabrolides A (3) and B (4) and prescabrolide (5). Chloroscabrolide A is a pentacyclic norcembranoid including an unprecedented THF-type ring to connect C-13 and C-15; furthermore, it is only the second chlorinated cembranoid derivative to be reported in the literature. The relative configuration of chloroscabrolide A has been established on the basis of a comparison between experimental ¹³C NMR data and DFT-calculated ¹³C NMR chemical shifts. All the isolated norcembranoids have been evaluated for iNOS protein inhibition.     

New Iridoid Glucosides and a Lignan Diglucoside from Globularia alypumL

The four new iridoid glucosides globularicisin (2) , globularidin (5) , globularimin (9) , and globularinin (13) , the lignan diglucoside liriodendrin (18) , and syringin (20) have been isolated from Globularia alypum L. along with the previously reported glucosides globularin (1) and catalpol (4) . Compound 2 is the first report of any cinnamoyl iridoid with a cis-configuration at the acyl double bond. Compound 5 is another novel iridoid which lacks the characteristic C(3), C(4) double bond in the aglucone part. Compounds 9 and 13 are diastereomeric and contain highly oxygenated aglucone structures. The isolation of liriodendrin, from Globularia alypum is the first demonstration of the occurrence of a lignan in the family Globulariaceae. The structures have been elucidated by ¹ H - and ¹³ C-NMR . spectroscopy as well as by chemical transformations. Taxonomical significance of the cooccurrence of iridoid and lignan glycosides as well as the antileukemic potentiality of the latter are also appraised.     

13C-NMR-Untersuchungen zur Strukturaufklärung von Polysacchariden und deren Methylderivaten

The ¹³C NMR spectra of some polysaccharides and their methyl derivatives have been analysed. The numbers and positions of the assigned ¹³C NMR signals give some information about the structure of the monomer unit and the positions of the glycosidic linkage but no information about the anomeric configuration. In this case the ¹J(C-1, H) coupling constants make it possible to identify the anomeric configuration, because the mean differences of the J values for the α- and β-anomers are 12 Hz (at least 5 Hz) with the higher values for the α-anomers.     

The structure of 1,6,6aλ4-trithiapentalene and substituted 1,6,6aλ4-trithiapentalenes studied by means of NMR spectroscopy

¹³C NMR spectra of unsubstituted 1,6,6aλ⁴-trithiapentalene and a series of methyl and phenyl substituted 1,6,6aλ⁴-trithiapentalenes have been recorded. The spectra have been assigned by comparison with ¹H NMR data based on coupling constants from undecoupled spectra. From the chemical shift of C-3a it is concluded that the double bond character of the C-3a—S-6a is low. The relaxation times for C-2 and C-3 only show small differences; this seems not to be in favour of a fast interconversion between two thiocarbonyl forms. The NMR data obtained seem thus to be in accordance with a bicyclic naphthalene-like structure with ten delocalised π-electrons.     

Investigation of the exo and endo isomers of dioxolane-type benzylidene derivatives of carbohydrates by 13C NMR spectroscopy

The absolute configurations of nine 2,3-O-benzylidene-α-L-rhamno- and α-D-mannopyranoside diasteteomeric pairs were determined and the ¹³C NMR spectra of further thirteen α-L-rhamno- and α-D-mannopyranosides, having various substituents, were completely assigned.Four ¹³C shifts were found suitable for the determination of the absolute configuration of the dioxolane skeleton. (1) The chemical shift of the acetal carbon in the endo isomers is between 103.9 and 104.7 ppm whereas for the exo isomers this region extends from 102.8 to 103.4 ppm; (2) The formation of the dioxolane ring causes a deshielding effect for the bridgehead carbons, in the exo isomers this effect is more pronounced for C-3 whereas in the endo isomers for C-2. For C-4, shielding effect was found in the exo isomers and deshielding effect in the endo ones; (3) The chemical shift of the quaternary carbon of the phenyl group is greater in the exo isomers than in the endo ones; (4) The difference between the shift of the acetal carbon and that of the quaternary carbon of the phenyl group in the exo isomers is greater than 35.4 ppm, in the endo isomers is less than 33.7 ppm.     

13C NMR investigation of flavonoid C-β-D-glucosides. Detection of a conformational equilibrium

Evidence of a slow conformational equilibrium in some flavonoid 6?C?β?D ?glucosides is deduced from examination of their ¹³C NMR spectra run at room temperature.     

Enantioselective total synthesis and correction of the absolute configuration of megislactone

The title compound, one of the constituents from Iryanthera megistophylla, has been synthesized in enantiopure forms. The stereogenic centers at C-2 and C-3 were constructed by using a chiral auxiliary induced asymmetric aldolization and the C-4 was derived from the corresponding optically active lactates. The carbon-carbon double bond in the side chain was derived from a pure cis vinyl iodide using a Suzuki coupling with an alkyl borane formed in situ from the corresponding terminal alkene. A previously unknown (partial) cis to trans transformation of an isolated C-C double bond in a long alkyl chain was observed during the deprotection of TBS group with CAN. Somewhat unexpectedly, the otherwise undetectable co-presence of the trans isomer of the remote double bond in a long alkyl chain was clearly revealed in ¹H and ¹³C NMR in the presence of a lactone ring. The present work unambiguously shows that the absolute configuration of the natural compound is the antipode of the one originally reported. Some errors in the previous ¹H and ¹³C NMR signal assignments are also corrected.     

Application of two-dimensional NMR spectroscopy to the complete analysis of the 1H and 13C NMR spectra of d-biotin in aqueous solution

The ¹H and ¹³C NMR spectra of d-biotin were observed at 400 and 100 MHz, respectively. Various types of two-dimensional NMR spectroscopy were performed to assign the spectra. The previous assignment of ¹³C NMR spectrum of d-biotin reported by Bradbury and Johnson was modified, and the dihedral angles between the C? H bonds of the ring were determined. The populations of the conformers produced by internal rotation around the C-2? C-δ bond were estimated.     

Carbon-13 NMR spectra of chlorophyll a,chlorophyll a′, pyrochlorophyll a and the corresponding pheophytins

The ¹³C NMR spectra of C-10 epimeric chlorophylls a and a′, pheophytins a and a′, pyrochlorophyll a and pyropheophytin a have been recorded and assigned by chemical shift comparison, by long-range selective ¹H decoupling experiments and by the examination of the fully coupled spectra. Various factors influencing the ¹³C chemical shifts of the chlorophyll derivatives, e.g. the coordination of magnesium to the chlorin nucleus, the effect of solvent and the steric strain at the periphery of the macrocycle, have been examined. The ¹³C NMR spectra of chlorophyll a measured in acetone-d₆ and tetrahydrofuran-d₈ (THF) were compared, and remarkable solvent effects on the ¹³C chemical shifts were observed. These effects were interpreted mostly in terms of specific chlorophyll-solvent interactions. Different electron donor and steric properties of acetone and THF were considered to cause conformational alterations in the macrocycle, induced by the ligation of the solvent molecule(s) to the axial position(s) of the central magnesium atom of chlorophyll a. These results show that ¹³C NMR spectroscopy is a method of high information value for investigations of the unique electron donor acceptor (EDA) properties of the chlorophylls. The structural differences between the C-10 epimeric chlorophylls and pheophytins were examined in terms of the substituent chemical shift (SCS) parameters for the C-10 methoxycarbonyl group. The analysis showed that the change from the (10R) to the 10(S) configuration induces conformational alterations in the whole macrocycle which are, however, most prominent in rings IV and V. Owing to the increased steric interaction (repulsion) between the bulky substituents at C-7 and C-10, the peripheral strain is larger in the (10S) form, and is relieved by more pronounced deviations of rings IV and V from the macrocyclic plane compared with the (10R) form. The examination of the SCS parameters also showed that the peripheral steric strain is dissipated to a larger extent over the entire macrocycle in the Mg-free derivatives. These results confirm the previous conclusions based on ¹H NMR and CD data. The possible function of chlorophyll a′ in photosynthesis is briefly discussed.     

Complete Solid State 13C NMR Chemical Shift Assignments for α-D-Glucose, α-D-Glucose-H2O and β-D-Glucose

Abstract

NMR spectra of crystalline α-D-glucose DH₂O (1), α-D-glucose (2), and β-D-glucose (3) were examined by 13C cross polarization magic angle spinning (CPMAS) methods. Each of the three forms of glucose exhibited a distinctly different spectrum. Chemical interconversion of 2 and 3 as well as the in situ dehydration of 1 during the course of the CPMAS NMR experiment was monitored in the ¹³C spectra. Samples of 1, 2, and 3 specifically enriched at C-1 and C-6 with ¹³C yielded ¹³C spectra in which the resonances corresponding to the adjacent C-2 and C-5 carbons were not visible due to strong homonuclear ¹³C dipolar interactions with the high abundance label. Spectra of these analogues as well as the C-2 and C-3 labeled materials provided the complete ¹³C chemical shift assignments of crystalline 1 2, and 3. A comparison of the solid state and solution ¹³C spectra revealed substantial resonance shifts for each of the three structures examined.     

13C NMR spectroscopy of 4,5- and 5,6-double bond isomers of spiro-3-steroidal ketone derivatives : The determination of the structures of steroidal thiazolidines

The thiazolidine isomers obtained upon the reaction of aminoethanethiols with α,β-unsaturated steroidal ketones were found to be double bond positional isomers based on their optical rotations and ¹H and ¹³C NMR spectra. The ¹³C NMR spectra of analogous ketals, hemithioketals and a thioketal of steroidal ketones were also reported, and ¹³C NMR spectroscopy was shown to be a convenient method of assigning the position of the double bond in the double bond isomers for all four of these derivatives. Finally, ¹³C NMR spectroscopy was found to be useful in determining that thiazolidine formation was stereospecific to give only one C-3-isomer.