Photochemistry of Biliverdin IX δ as a model for the study of the photoproducts from natural biliverdin IXγ (pterobilin)

The configurations of biliverdin-IX_γ and -IX_δ dimethyl esters 1 and 2 in solutions, have been studied using Nuclear-Overhauser-Effect (NOE) experiments. Irradiation (500-700 nm) of biliverdin IXδ gave syn-Z → anti-E isomerization of the central methine bridge and in aerated polar solutions, four new cyclized pigments were isolated for which structures 3, 4, 5 and 6 are proposed. Neobiliverdin IXδ 3 is also formed in degassed solution (Φ=4.10^?5) but pigments 4, 5 and 6 arise from photo-oxidation with O₂. Biliverdin IXδ appears to be a good model for the study of photo-reactions occurring on the vinyl groups of the natural biliverdin IXγ (pterobilin).     

A contradistinction in the magnetic (13C NMR spectroscopy) and chemical behaviour of 4-Oxo-4,5,6,7-tetrahydroindole derivatives

Carbon-13 NMR data are reported for a series of 1,2-diaryl-4-oxo-4,5,6,7-tetrahydroindoles, 6-methyl-2-phenyl-4-oxo-4,5,6,7-tetrahydrobenzofuran and 1-,6-dithiaindan-4-one. The chemical shifts δ 193–196, δ 195.5 and δ 184 are identified for the carbonyl carbon (C-4) in the tetrahydroindoles, tetrahydrobenzofuran and dithiaindan derivatives, respectively. These shifts are located in the same region as that reported for the corresponding carbonyl carbon in aryl conjugated ketones. An excellent correlation between the chemical shift for the carbonyl carbon and the chemical reactivity of the ketonic function is noticed in the case of the latter two series of ketones while such a correlation is typically absent in the case of the 4-ketotetrahydroindole derivatives.     

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.     

Molecular spectra and molecular structure of heterocyclic compounds. Infrared and near ultraviolet absorption spectra of pyridine N-oxide derivatives

The infrared and ultraviolet spectra of many pyridine N-oxide derivatives have been studied. Ultraviolet spectra show a strong solvent effect in going from aprotic to hydroxylic solvents due to strong hydrogen bonding. Values of δ H° for several systems CH₃OH/XPyNO in tetra-chloroethylene solution were evaluated by infrared techniques and a linear correlation δ H° vs. δ v OH has been found. Features of the infrared and ultraviolet characteristic absorption bands were also investigated.     

On the synthesis and reactivity of 4,10-dihydrobenzo-[b]thieno[2,3-e]thiepin-10-acetic acid and 5,10-dihydrobenzo[e]thieno[3,2-b]thiepin-10-acetic acid

A simple method to synthesize 4,10-dihydrobenzo[b]thieno[2,3-e]thiepin-10-acetic acid (8a) and 5,10-dihydrobenzo[e]thieno[3,2-b]thiepin-10-acetic acid (8b) starting from ketones la,b is described. The reactivity of the acid 8a has been investigated and some derivatives are reported.     

Die synthese von bis-(p-methoxyphenyl)- und bis-(p-nitrophenyl)-keten und deren verhalten gegenüber sauerstoff und nucleophilen reagenzien

The synthesis of bis-(p-methoxyphenyl)-ketene (IX) and of bis-(p-nitrophenyl)-ketene (VI) from the corresponding aril-monohydrazones is described. Whereas IX could be isolated in pure crystalline form, VI had to be prepared as a solution. Addition of methanol to diphenylketene (III) proceeds 1.6 times faster than to dianisylketene (IX). Bis-(p-nitrophenyl)-ketene (VI) is considerably more reactive towards water than either III or IX; a quantitative determination of its relative reactivity was not possible. Dianisylketene reacts approximately 15 times faster with molecular oxygen and yields 4 times more of the corresponding diarylketone and carbon dioxide than do the ketenes III and VI. It is shown with ¹⁸O₂ that molecular oxygen is indeed involved in the oxidation of dianisylketene to dimethoxybenzophenone and carbon dioxide.     

Carbon-13 NMR spectra of a series of para-substituted N,N-dimethylbenzamides. Comparisons of linear free energy relationships for carbon-13 and nitrogen-15 chemical shifts and rotation barriers

All carbon-13 chemical shifts for 11 para-substituted N,N-dimethylbenzamides in 1 mole % chloroform solution are reported, with assignments based upon double resonance experiments, analogy to chemical shifts of benzamide, and self-consistency between experimental and calculated values using recognized substituent parameters. In contrast to earlier reports, the aryl carbon chemical shift assignments for N,N-dimethylbenzamide are C-2, 127.0; C-3, 128.7; C-4, 129.4, and for p-chloro-N,N-dimethylbenzamide are C-1, 134.6; C-4, 135.5 ppm, relative to internal TMS. Good Hammett correlations (σ_p) are reported for ¹³C chemical shifts of C-1 (σ = 11.9 ppm) and even for the carbonyl group (σ = ?2.3 ppm) but are markedly improved if correlated with σ_p+ (σ = 9.5 ppm) and Dewar's F (σ = ?1.9 ppm), respectively. Excellent Swain–Lupton F and R correlations were found for some of the ¹³C chemical shifts and yielded values for percent resonance contributions to transmission of substituent effects as follows, C-1, 75 ± 4%; C-2, 51 ± 3%; C?O, 31±2%. These are compared to similar values calculated from the C?O of benzoic acids of 34±10%, and from the nitrogen-15 chemical shifts of benzamides of 56±2%. Correlations of these ¹³C δ values and ¹⁵N δ values with rotation barriers (ΔG) for N,N-dimethylbenzamides were examined, and it was found that while C?O δ values correlated only poorly the C-1 δ values correlated very well, but the best correlation was for ¹⁵N δ values of benzamides. It is suggested that Δ G and δ ¹⁵N are intrinsically related due to their numerical correlation, and the close similarity in percent resonance contribution of substituent influence on these parameters.     

Preparation and reactivity of 5‐substituted azepino[3,4‐b]indoles

Preparation of the 5‐substituted azepino[3,4‐b]indole core structure can be realised through a catalytic Heck reaction. The scope and limitations of this methodology are reported. The reactivity of di‐tert‐butyl 5‐ethoxycarbonylmethylene‐1,3,4,5‐tetrahydro‐1‐oxoazepino[3,4‐b]indole‐2,10‐dicarboxylate (1) was investigated in order to prepare the indole analogue of hymenialdisine and derivatives.     

Cyclization reactions of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole

The reaction of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole I with nitrous acid affords the azide III which could be cyclized with acetic anhydride to 10-acetyl-10H-tetrazolo[5′,1′:3, 4][1, 2, 4]triazino[5, 6-b]indole IIb . Cyclization reactions of I with acetic anhydride, ethyl chloroformate, carbon disulphide and aromatic aldehydes to the corresponding fused triazolo derivatives V–VIII are reported. On the other hand cyclization reactions of I with malononitrile, ethyl cyanoacetate, ethyl acetoacetate and acetylacetone to the corresponding condensed pyrazolino derivatives IX–XI are also reported. The reaction of I with α-dicarbonyl compounds to form mono and dihydrazones are reported. The structure of the compounds prepared and their cyclization mechanisms are reported.     

New routes to aroylthiadiazolines and arylazothiazoles from phenylglyoxalyl bromide arylhydrazones and phenacyl thiocyanate

Reaction of phenylglyoxalyl bromide arylhydrazones (III) with thiourea in ethanol produces 2-amino-4-phenyl-5-arylazothiazoles (XI) instead of the expected 2-benzoyl-4-aryl-5-imino-Δ^2?1,3,4-thiadiazolines (V) obtained from III and potassium thiocyanate. Phenacyl thiocyanate (IV) couples with diazotized anilines to give V. The mechanisms of formation of V and XI from VI and III, respectively, are postulated. Nitrosation of V gives the corresponding N-nitroso derivatives (VII), which decompose upon refluxing in xylene to give 2,4-disubstituted Δ² ?1,3,4-thiadiazolin-5-ones (VIII). The thiadiazolines V give the respective N-aeyl derivatives IX and X with acetic anhydride and benzoyl chloride in pyridine.     

Three polymorphs (α, β, and δ) of d‐mannitol at 100 K

In the monoclinic δ polymorph of d ‐mannitol, C₆H₁₄O₆, both the mol­ecule and the packing have approximate twofold rotational symmetry. The P2₁ structure thus approximates space group C222₁, and the α′ polymorph, previously reported in that space group, is almost certainly identical to the δ polymorph. However, torsion angles along the main backbone of the mol­ecule deviate from twofold symmetry by as much as 7.4 (3)° and the hydrogen‐bonding pattern does not conform to the higher symmetry. The α polymorph reported here is identical to the previously reported κ polymorph, and the low‐temperature structure of the β polymorph agrees well with previously reported room‐temperature determinations. The range of C—O bond lengths over the three polymorphs is 1.428 (2)–1.437 (4) Å, and the range of C—C distances is 1.515 (4)–1.5406 (19) Å. The δ polymorph has the highest density of the three, both at room temperature and at 100 K.     

Syntheses and tandem Diels-Alder reactivities of 7,7-diphenyl-[2.2.1]hericene (= 7-(diphenylmethylidene)-2,3,5,6- tetramethylidenebicyclo[2.2.1]heptane) and 7-oxa[2.2.1]hericene ( = 2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)

Syntheses of 7,7-diphenyl[2.2.1]hericene ( 4 ) and 7-oxa[2.2.1]hericene ( 5 ) are presented. Rate constants k₁ and k₂ of the two successive Diels-Alder additions of ethylenetetracarbonitrile (TCE) to 4 and to 5 have been evaluated. At 25° in toluene, the rate-constant ratio k₁/k₂ = 260 and 21 for 4 and 5 , respectively. These results are compared with those reported for the tandem Diels-Alder reactivity of 2,3,5,6-tetramethylidenebicyclo[2.2.1]heptane and other derivatives.     

Carbon-13 n.m.r. of the 8-phosphabicyclo[3.2.1]octane system

¹³C Chemical shifts and ¹³C? ³¹P nuclear spin coupling constants have been determined for 26 8-phosphabicyclo[3.2.1]octane derivatives, namely phosphines, phosphine oxides, phosphine sulphides and one phosphonium salt. The influence of the phosphorus configuration on δ and ²J(PC) values was examined and other factors influencing the ²J(PC) coupling constant are discussed.     

Investigations on the Synthesis,Reactivity, and Properties of Perfluoro-α-Benzo-Fused BOPHY Fluorophores

The synthesis and reactivity of 3,8-dibromo-dodecafluoro-benzo-fused BOPHY 2 are reported, via S_NAr with O-, N- S- and C-nucleophiles, and in Pd(0)-catalyzed cross-coupling reactions (Suzuki and Stille). The resulting perfluoro-BOPHY derivatives were investigated for their reactivity in the presence of various nucleophiles. BOPHY 3 displays reversible color change and fluorescence quenching in the presence of bases (Et₃N, DBU), whereas BOPHY 7 reacts preferentially at the α-pyrrolic positions, and BOPHY 8 undergoes regioselective fluorine substitution in the presence of thiols. The structural and electronic features of the fluorinated BOPHYs were studied by TD-DFT computations. In addition, their spectroscopic and cellular properties were investigated; BOPHY 10 shows the most red-shifted absorption/emission (λ_max 659/699 nm) and 7 the highest fluorescence (Φ_f=0.95), while all compounds studied showed low cytotoxicity toward human HEp2 cells and were efficiently internalized.     

Cleaner Citral Condensation - Synthesis of Pyrano [2,3-a] Carbazoles

Citral condensation¹ with phenols are characterized by the formation of multitudinous products, poor yields and unpredictable course as evidenced by conflicting reports.^2,3 They are sensitive to temperature and amount of catalyst -usually pyridine - used.⁴ In the attempts to synthesize pyrano [2,3-a] carbazole derivatives isomeric with Mahanimbine⁵ (I), a representative C-23 pyrano [3,2-a] carbazole alkaloid, the usual pyridine catalysed citral condensation was tried but the expected pyranocarbazole derivatives could not be isolated in pusstate. The reaction of l-hydroxy-6-methylcarbazole with citral in pyridine, for instance, gave a product on chromatographic purification followed by micro-distillation at 195–200° (bath)/0.01 mm. Though homogeneous on TLC, it indicated the presence of atleast two closely related pyranocarbazole derivatives when its PMR spectrum was examined. It showed two deuterium exchangeable protons at δ 7.86 and δ 8.00. The olefinic protons appeared as doublet of doublets at δ 5.52 and δ 6.52. Addition of benzoic acid (2% of thecatalyst) as recommended⁶ gave no better results.     

(α-Phosphoryl Carbanions. Searching of Course of Wittig-Horner Reaction by 31P Low Temperature NMR

Abstract

Continuing our studies on utilization of the Wittig-Horner reaction in organic synthesis, we have examined reactivity of α-lithium derivatives of several phosphonates towards carbonyl compounds, by ³¹P NMR at low temperature (from -100°C to r.t.). The chemical shifts δ [ppm] of a few representative phosphonates (1), carbanions (2) and betains (3) will be given.     

Pteridines. Part LXXXV. Chemical synthesis of deoxysepiapterin and 6-acylpteridines by acyl radical substitution reactions

A new synthesis of deoxysepiapterin ( 2 ), one of the two yellow eye pigments of the Drosophila mutant sepia, is described. The synthetic approach makes use of a homolytic nucleophilic acylation of 7-(alkylthio)pteridine derivatives ( 11, 13, 15, 18, 20 ) leading to the corresponding 6-acyl derivatives ( 21–27 ). Desulfurizations have been achieved for the first time in the pteridine series using Raney-Co,Raney-Cu, or Cu? Al alloy in alkaline medium. Besides cleavage of the C(7)? S bond, further reductions of the C?O group at C(6) and the C(7)?N(8) bond are detected as side reactions leading to 6-(1-hydroxyalkyl) ( 34, 35, 42, 43 ) and 6-acyl-7,8-dihydro derivatives ( 2, 36, 37 ), respectively, The newly synthesized compounds have been characterized by elemental analysis, p_K determination, UV and ¹H-NMR spectra.     

Polycyclic N-hetero compounds. XXIX. Synthesis and antidepressive evaluation of 15-thia-11,13-diazasteroidal analogues and their precursors

Syntheses of novel 15-thia-11,13-diazasteroidal skeleton IV and its D-homo analogues are described. Meso-ionic derivatives of IV were also synthesized. Antidepressive activities of these compounds and their precursors were screened. D-Dihomothiadiazasteroid IX and 3,4,5,6-tetrahydrobenzo[h]quinazoline-4-thione ( V ) exhibited antireserpine action.     

Synthesis and characterization of polymers from itaconic acid derivatives

Some itaconic acid derivatives were prepared and polymerized, in which itaconic acid (IA), β-monoalkyl itaconates (mRI), dialkyl itaconates (DRI), N-substituted itaconamates (IAE), itaconamides (IAm), itaconic anhydride (IAn), N-alkylitaconimides (RII), and N-(alkyl-substituted phenyl)itaconimides (RPhII) are included. The polymerization reactivity was examined, and discussed in relation to the structure of the monomers. The structure and some properties of the resulting polymers were investigated. Some citraconic acid (CA) and mesaconic acid (MA) derivatives were also polymerized, and their reactivities were compared with the corresponding IA derivatives.