A 1H-NMR Spectroscopic Investigation of the Conformation of the Acetamido Group in Some Derivatives of N-Acetyl-D-allosamine and -D-glucosamine

The population of the conformations obtained by rotation around the C(2)? N and the N? C(O) bonds of AllNAc, GlcNAc, and GlcNMeAc derivatives was investigated by ¹H-NMR spectroscopy. The AllNAc-derived α-D -and β-D -pyranosides 4–7 , the AllNAc diazirine 16 , and the GlcNAc-derived axial anomers α-D - 8–10 prefer the (Z)-anti-conformation. A significant population of the (Z)-syn-conformer in the (Z)-syn/(Z)-anti-equilibrium for the equatorial anomers β-D - 8–10 and the GlcNAc diazirine 17 was evidenced by an upfield shift of H? C(2), downfield shifts of H? C(1) and H? C(3), and by NOE measurements. The population of the (Z)-syn-conformation depends on the substituent at C(1) and is highest for the hexafluoroisopropyl glycoside. The population of the (Z)-syn-conformation of β-D - 14 decreases with increasing polarity of the solvent, but a substantial population is still observed for solutions in D₂O. Whereas the α-D -anomers of the hemiacetal 22 and the methyl glycoside 21 prefer the (Z)-anti-conformation in D₂O solution, the corresponding β-D -anomers are mixtures of the (Z)-anti-and (Z)-syn-conformers. The diazirine 17 self-associates in CD₂Cl₂ solution at concentrations above 0.005M at low temperatures. The axial anomers of the GlcNMeAc derivatives α-D - 26–28 are 2:1 to 3:1 mixtures of (Z)-anti-and (E)-anti-conformers, whereas the corresponding β-D -glycosides are ca. 1:3:6 mixtures of (Z)-syn-, (Z)-anti-, and (E)-anti-conformers.     

1,5-Stereocontrol in tin(IV) halide mediated reactions between N- and S-substituted pent-2-enylstannanes and aldehydes or imines

Following transmetalation of (4S)-4-(dibenzylamino)pent-2-enyl(tributyl)stannane with tin(IV) bromide, reactions of the resulting allyltin tribromide with aldehydes gave (3Z)-1,5-syn-5-(dibenzylamino)hex-3-en-1-ols with excellent, ca. 98:2, stereocontrol. (4R)-5-Benzylthio-4-methylpent-2-enyl(tributyl)stannane similarly reacted with aldehydes to give (3Z)-1,5-anti-6-benzylthio-5-methylhex-3-en-1-ols with 87:13 stereocontrol. Although the analogous reaction of (4R)-4-benzylthiopent-2-enyl(tributyl)stannane with benzaldehyde proceeded with some stereoselectivity, 80–90:20–10, in favour of the (3Z)-1,5-syn-diastereoisomer, the yield was low due to a competing Lewis acid catalysed 1,4-elimination. N-Acylamino- and S-acylthio-pent-2-enylstannanes reacted with aldehydes with variable syn/anti-stereoselectivities. Tin(IV) chloride promoted reactions of the 4-(dibenzylamino)pent-2-enylstannane with 1-alkoxycarbonylimines gave (E)-alk-4-enoates with a modest preference for the 2,6-anti-products, 2,6-anti/2,6-syn=75:25.     

On the chemistry of pyrrole pigments,XCVII: Synthesis,stereochemistry, and solvatochromic effects of a 1-(dipyrrinon-9-yl)-3-(dipyrrinon-9-ylidene)-1-propene

Summary By condensing a dipyrrinon-9-yl-acrolein with a dipyrrinone unsubstituted in position 9, an unsymmetricb-vinylogous verdinoid pigment was prepared. The configuration of this molecule was elucidated by means of 2D¹H NMR experiments to be (4Z,10E,12Z,17Z) in solutions of chloroform and dimethylsulfoxide, and its conformation was derived to be 5syn,9syn,11anti,16syn. The pronounced solvatochromic effect of this molecule with a cyclic helical geometry could be explained by solvent induced conformational changes.

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Zur Chemie von Pyrrolpigmenten, 97. Mitt.: Synthese, Stereochemie und Solvatochromer Effekt eines 1-(Dipyrrinon-9-yl)-3-(dipyrrinon-9-yliden)-1-propens

Zusammenfassung Durch Kondensation eines Dipyrrinon-9-yl-acroleins mit einem in Position 9 unsubstituierten Dipyrrinon wurde ein unsymmetrischesb-vinyloges verdinoides Pigment dargestellt. Die Konfiguration dieses Moleküls wurde mit Hilfe von 2D-¹H-NMR-Experimenten in Lösungen von und Dimethylsulfoxid als (4Z,10E,12Z,17Z) abgeleitet; seine Konformation konnte zu 5syn,9syn,11anti,16syn festgelegt werden. Die ausgeprägte Solvatochromie dieses Moleküls mit cyclisch helikaler Geometrie konnte auf solvensinduzierte konformative Veränderungen zurückgeführt werden.

     

NMR of enaminones. Part 7 1H-, 13C-, and 17O-NMR and X-ray structure determinations of 1,2-disubstituted conjugated 3-[(tert-Butyl)amino]enones

¹H-, ¹³C-, and ¹⁷O-NMR spectra for the 2-substituted enaminones MeC(O)C(Me)?CHNH(t-Bu) ( 1 ), EtC(O)C(Me)?CHNH(t-Bu) ( 2 ), PhC(O)C(Me)?CHNH(t-Bu) ( 3 ), and MeC(O)C(Me)?CHNH(t-Bu) ( 4 ) are reported. These data show that 3 exists mainly in the (E)-form, 4 in (Z)-form, and 1 and 2 as mixtures of both forms. Polar solvents favour the (E)-form. The (Z)- and (E)-forms exist in the 1,2-syn,3,N-anti and 1,2-anti,1,N-anti conformations A and B , respectively. The structures of the (E)- and (Z)-form are confirmed by X-ray crystal-structure determinations of 3 and 4. The shielding of the carbonyl O-atom in the ¹⁷O-NMR spectrum by intramolecular H-bonding (Δλ_HB) ranging from ?28 to ?41 ppm, depends on the substituents at C(l) and C(2). Crystals of 3 at 90 K are monoclinic. with a = 9.618(2) Å, b = 15.792(3) Å, c = 16.705(3) Å, and β = 94.44(3)°, and the space group is P2₁/c with Z = 8 (refinement to R = 0.0701 on 3387 independent reflections). Crystals of 4 at 101 K are monoclinic, with a = 16.625(8) Å, b = 8.637(6) Å, c = 11.024(7) Å, and β = 101.60(5)°, and the space group is Cc with Z = 4 (refinement to R = 0.0595 on 2106 independent reflections).     

Conformation and Crystal Structure of Dipyrrinones with Oxindole Components

 Pyrrole α-aldehydes (2-formyl-4,5-dimethyl-1H-pyrrole and 2-formyl-N-methylpyrrole) condense readily at C(3) of indolin-2-ones to give dipyrrinone analogs, such as (3Z)-[(4,5-dimethylpyrrol-2-yl)-methylidenyl]-indolin-2-one and (3E)-[(1-methylpyrrol-2-yl)-methylidenyl]-indolin-2-one. ¹H-NMR NOE analyses and X-ray crystallography confirm the syn-(Z) configuration for the former and the syn-(E) configuration for the latter. The former is stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations of the latter indicate no energy difference between the syn and anti conformations.     

Preference for Syn Ene Additions of 1O2 to Trisubstituted,Acyclic Olefins

Dye-sensitized photooxygenations of 3 pairs of (E)/(Z) trisubstituted olefins were studied in order to establish the partitioning between the 3 possible ene additions. The (E)-isomers underwent only the 2 ene additions (>95%) involving H-atom abstractions at the same, disubstituted side of the olefins, termed syn ene additions, with almost equal ease. The (Z)-isomers underwent mainly (85-90%) the syn ene additions, with the ones leading to the tertiary hydroperoxides distinctly favoured, and some (10-15%)ene additions at the monosubstituted side of the olefin, termed anti ene addition.     

Stereoselectivity in the anionic oxy-Cope rearrangement of acyclic vinyl sulfides

Novel anionic oxy-Cope (AOC) rearrangements of substituted 5-alkylthio-1,5-dien-3-ols were studied. Aqueous quench gave new access to compounds with a nucleophilic vinyl sulfide and an electrophilic aldehyde in a 1,5 relationship. 3,4-Anti and 3,4-syn 1E,5Z-5-hexylthio-4-methyl-1-phenylhepta-1,5-dien-3-ols were synthesised separately by stereoselective aldol reaction, thioesterification and alkylidenation of the resulting thioesters to give Z-vinyl sulfides with ?90% stereoselectivity. AOC rearrangement of the 3,4-syn substrate gave predominantly 3,4-syn Z-vinyl sulfide while the 3,4-anti substrate gave mostly 3,4-syn E-vinyl sulfide, via chair-like transition states with the oxyanion pseudo-equatorial. Stereochemistry was assigned by NOE taking advantage of the conformational stability of the products.     

Addition of γ-silyloxyallyltins on ethyl glyoxylate: evaluation of the influence of the experimental conditions on the stereochemical course of the reaction

Ethyl glyoxylate was reacted with α-substituted γ-(t-butyldimethylsilyloxy)-allyltributyltin in order to obtain selectively each diastereomer of ethyl 3-(t-butyldimethylsilyloxy)-2-hydroxyhex-4-enoate and subsequently the corresponding diols. Diastereomers syn-E, anti-E and anti-Z were obtained in good yields with good to high selectivities and the obtained results were rationalized by consideration of cyclic or open transition states in agreement with the experimental conditions and with the structure of the starting reagents.     

Zur Chemie der Pyrrolpigmente, 63. Mitt.

Using hexamethylphosphoric acid triamide (HMPT) as solvent for bilatrienesabc and mainly for 2,3-dihydrobilatrienes-abc (which serve as the most suitable models for the biliproteid chromophores) a small hypsochromic shift and a dramatic change of the relative intensities of short and long wavelength absorption bands, as compared to solutions in CCl₄, is observed. Applying NMR-spectroscopic techniques (¹⁵N-,¹³C-,¹H-) a predominance of the (4Z,9E,15Z) diastereomer forming a 5syn-, 10anti-, 14syn-periplanar orclinal conformation is deduced. The stabilisation of this configuration and conformation arises from strong hydrogen bonds between the acidic protons of the bilins andHMPT. Interactions of this kind seem to be the main source of energy to stretch the otherwise coiled bilin chromophore of (4Z,9Z,15Z)-5sp,10sp,14sp geometry. Stretched systems of the type bilin-HMPT may serve as a valuable model for the natural biliproteides.

Herrn Prof. Dr.A. Eschenmoser zum 60. Geburtstag gewidmet.116, 1065 (1985).     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

ss‐NMR and single‐crystal X‐ray diffraction in the elucidation of a new polymorph of bischalcone (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one

We report a new polymorph of (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one, C₁₇H₁₂F₂O. Contrary to the precedent literature polymorph with Z′ = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so‐called anti or syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half‐occupied and overlapping molecules presenting both anti and syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C—H…O contacts involving the carbonyl and anti‐oriented β‐C—H groups, which is reflected in three ¹³C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.     

The adamantane rearrangement of syn- and anti-Tricyclo[4.2.1.1.12,5] decane. Part II. Rearrangements initiated by regioselective formation of carbocations at C(3) and C(9)

The endo- and exo-alcohols 5–12 of syn-( 1 ) and anti-tricyclo[4.2.1. 1^2.5]decane ( 2 ) were treated with BF₃/Et₃SiH (ionic hydrogenation) in order to study the behaviour of the corresponding regioselectively generated carbocations at C(3) ( a (syn), b (anti)) and C(9) ( c (syn), d (anti)). The anti-hydrocarbon 2 is practically the sole product obtained starting with the four 3-alcohols (via a → b from 5 and 6 (syn) and via b from 9 and 10 (anti)). The four 9-alcohols in each case yield a mixture of 2-endo, 3-endo- ( 3 ) and 2-exo,3-exo-trimethylene-8,9,10-trinorbornane (4) (via c → e from 7 and 8 (syn) and via d → f from 11 and 12 (anti)), but no hydrocarbon 2 , i.e. none of the 1,3-H shifts c → a and d → b is involved.     

Conformation and Crystal Structure of Dipyrrinones with Oxindole Components

Summary.  Pyrrole α-aldehydes (2-formyl-4,5-dimethyl-1H-pyrrole and 2-formyl-N-methylpyrrole) condense readily at C(3) of indolin-2-ones to give dipyrrinone analogs, such as (3Z)-[(4,5-dimethylpyrrol-2-yl)-methylidenyl]-indolin-2-one and (3E)-[(1-methylpyrrol-2-yl)-methylidenyl]-indolin-2-one. ¹H-NMR NOE analyses and X-ray crystallography confirm the syn-(Z) configuration for the former and the syn-(E) configuration for the latter. The former is stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations of the latter indicate no energy difference between the syn and anti conformations. Corresponding author. E-mail: lightner@scs.unr.edu Received August 2, 2002; accepted August 30, 2002     

PHYTOCHROME MODELS,PART 9. CONFORMATION SELECTIVITY OF THE PHOTOCYCLIZATION OF THE BILIVERDIN IX γ and IX δ DIMETHYL ESTERS*

Abstract— The photocyclization of the biliverdin IX γ and IX δ dimethyl esters to phorcabilin and neobiliverdin IX δ dimethyl ester, respectively, markedly depends on the irradiation wavelength within the first electronic absorption band. The quantum yields of reaction are highest on irradiation at575–600 nm. As judged from fluorescence excitation studies, absorption by the stretched conformations of the biliverdins is relatively important at these wavelengths. At longer wavelengths, where the reaction efficiency sharply declines, absorption by the coiled form predominates. Based on these findings and on supporting evidence from the solvent and temperature influence on the reaction, the photocyclization is proposed to occur selectively from a stretched conformation (an example of the principle of nonequilibration of excited rotamers), competing with E-Z isomerization of the centralC–10 double bond. A kinetic hydrogen isotope effect on the photochemical reaction rate of N,N,N-trideuteriated biliverdin IX δ dimethyl ester indicates that the primary photoproduct in the cyclization reaction is labile and reacts via two competing processes: reopening to the starting material and a solvent-mediated proton shift. The latter process leads to the phorcabilin and neobiliverdin IX δ esters. The results suggest, as a general rule, that the stretching of coiled biliverdins is confined to thermal and photochemical transformations within the B/C partial structure, while the Z-syn geometry of the A/B and C/D moieties is retained.     

Study of conformations and hydrogen bonds in the configurational isomers of pyrrole‐2‐carbaldehyde oxime by 1H, 13C and 15N NMR spectroscopy combined with MP2 and DFT calculations and NBO analysis

The ¹H, ¹³C and ¹⁵N NMR studies have shown that the E and Z isomers of pyrrole‐2‐carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole‐2‐carbaldehyde oxime is stabilized by the N? H···N and N? H···O intramolecular hydrogen bonds, respectively. The N? H···N hydrogen bond in the E isomer causes the high‐frequency shift of the bridge proton signal by about 1 ppm and increase the ¹J(N, H) coupling by ～3 Hz. The bridge proton shows further deshielding and higher increase of the ¹J(N, H) coupling constant due to the strengthening of the N? H···O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by ～3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of ¹H shielding and ¹J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N? H···N and N? H···O hydrogen bondings to be estimated. The NBO analysis suggests that the N? H···N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N? H bond through the N? H···O hydrogen bond occurs in the Z isomer. Copyright © 2010 John Wiley & Sons, Ltd.     

(6R,9′Z)-Neoxanthin: Synthese,Schmelzverhalten, Spektren und Konformationsberechnungen

(6R,9′Z)-Neoxanthin: Synthesis, Physical Properties, Spectra, and Calculations of Its Conformation in Solution The synthesis of pure and crystalline (9′Z)-neoxanthin ( 6 ) is described. MnO₂ Oxidation of (9Z)-C₁₅-alcohol 7 at room temperature produces a mixture 8/9 of (9Z)- and (9E)-aldehydes. Predominant formation of the required (9Z)-aldehyde 8 is achieved by performing the oxidation at ? 10°. Condensation of 8 with the mono-Li salt of the symmetrical C₁₀-diphosphonate 10 gave the (9Z)-C₂₅-monophosphonate 11 . The Wittig-Horner condensation of 10 with the allenic C₁₅-aldehyde 1b , under selected conditions allows the preparation of pure and crystalline (9′Z)-15,15′-didehydroneoxanthin ( 12 ) and, after subsequent semireduction, of crystalline (15Z,9′Z)-neoxanthin ( 13 ). Thermal isomerisation of a AcOEt solution of 13 at 95° yields preferentially (9′Z)-neoxanthin ( 6 ). Our crystalline sample shows the highest ?-values in the UV/VIS spectra ever recorded. The CD spectra display a pronounced similarity with those of corresponding violaxanthin isomers. In contrast to the (all-E)-isomer 5 , (9′Z)-neoxanthin undergoes very little isomerisation when heated to its melting point. For comparison purposes, a crystalline probe of 6 is also isolated from lawn mowings. Extensive ¹H-and ¹³C-NMR investigations at 600 MHz of a (D₆)benzene solution using 2D-experiments such as COSY, TOCSY, ROESY, HMBC, and HMQC techniques permit the unambiguous assignment of all signals. Force-field calculations of a model system of 6 indicate the presence of several interconverting conformers of the violaxanthin end group, 66% of which possess a pseudoequatorial and 34% a pseudoaxial OH? C(3′). The torsion angle (ω₁) around the C(6′)? C(7′) bond, known to be of prime importance for the shape of the CD spectra, varies with values of 87° for 55% and 263° for 45% of the molecules. Therefore, the molecules clearly display a preference for the ‘syn’-position of the C(7′)?C(8′) bond and the epoxy group. Unexpectedly, the double bonds of C(7′)?C(8′) and C(9′)?C(10′) are not coplanar. The deviation amounts to ± 20°, both in the ‘syn’ - and the ‘anti’-conformation.     

Effect of ring fusion stereochemistry on double bond geometry. Unexpected formation of nine-membered cyclic ether with E-configurated double bond through RCM

Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating.     

A theoretical study of porphyrin isomers and their core-modified analogues: cis-trans isomerism, tautomerism and relative stabilities

Semiempirical (AM1 and PM3) and density functional theory (DFT) calculations were performed on about 50 porphyrin isomers with 25 each of 1,2 (syn) and 1,3 (anti) tautomeric forms. The corresponding oxa-and thia-core-modified analogues were also computed. The variations of relative energies and stabilities of the core-modified analogues were compared with parent porphyrin1 and the corresponding oxa-and thia-analogues. The trends in relative energies are not significantly changed while going from parent system to oxa-and thia-core-modified porphyrins in case of bothsyn andanti tautomers. Isomers of types [2·2·0·0], [3·0·1·0], [3·1·0·0], and [4·0·0·0] are destabilized due to the absence of methine bridge, which results in angle strain for tetrapyrroles. Isomers having [2·1·1·0], [2·1·0·1], [2·0·2·0] and [2·2·0·0] connectivity, the Z isomers, are more stable compared to the correspondingE isomers in bothsyn andanti forms of parent and core-modified analogues.     

PHYTOCHROME MODELS: PART 10. CONCENTRATION,SONICATION AND TEMPERATURE AFFECTING THE POPULATION OF THE GROUND-STATE CONFORMERS OF BILIVERDIN DIMETHYL ESTER IN SOLUTION*

UV-vis absorption and fluorescence spectroscopy were used to show that in alcoholic solutions (methanol, ethanol, 2-methylbutan-1-ol, and 2-octanol) concentration, temperature, and sonication affect the relative populations of the more rigid stretched and the more flexible helically coiled conformers of biliverdin dimethyl ester. In aromatic solvents, e.g. toluene, no such effects could be detected. At concentrations larger than 3 10^-5M in the alcoholic solvents aggregates and monomeric coiled species prevail. Upon dilution, the fraction of stretched monomeric conformers increases. Heating and sonication at concentrations smaller than 3 10^-5M further and irreversibly increase the fraction of the stretched conformers. The activation parameters for this change are compatible with the assessment that no equilibrium is attained between the two families of conformers even after several hours at room temperature, since the barriers arc higher than kT at this temperature. The present results and those previously reported on the excited-state processes of biliverdin dimethyl esters are explained on the basis of a scheme in which the eight possible ring B/C isomers of biliverdin dimethyl ester are interconverted through intra-and intermolecular proton transfers, rotations around C-C single bonds, and E-Z photoisomerizations around C = C double bonds.     

The Aluminum-Bromide-Catalyzed Adamantane Rearrangement of syn- and anti-Tricyclo[4.2.1.12,5]decane

In the presence of AlBr₃ in CS₂ at temperatures below 0°, syn-tricyclo[4.2.1.1^2,5]decane ( 1 ) isomerizes exclusively to anti-tricyclo[4.2.1.1^2,5]decane ( 2 ) at a higher rate than the latter rearranges to 2-exo,3-exo-trimethylene-8,9,10-trinorbornane ( 4 ). However, at temperature above 0°, the anti-isomer 2 isomerizes to 4 faster than 1 to 2 and 4 . As a consequence, hydride abstraction occurs at C(3) (→carbocation a , which rearranges to carbocation b (anti-skeleton)) in the syn-isomer 1 , and more readily at C(9) (→carbocation c ) than at C(3) (→carbocation b ) in the anti-isomer 2 .