The charge delocalised beta,beta-carotene dication--preparation, structure elucidation by NMR and reactions with nucleophiles

The reaction between beta,beta-carotene and BF3-etherates has been investigated, leading to structural elucidation of the blue product, formed in appropriate organic solvents, as a symmetrical charge delocalised dication (lambda(max) 985 nm at room temperature in CHCl3) with considerable stability. The reaction, monitored by EPR studies at -25 degrees C, occurred via free radical intermediates. A C40H56BF3 intermediate was captured by EIMS. The detailed structure of the dication was established by COSY, HSQC, HMBC and 1D and 2D ROESY NMR techniques (600 MHz, CDCl3, -20 degrees C) leading to complete assignments of 1H and 13C chemical shifts and 3J(H,H) coupling constants. The effects of the two delocalised charges on chemical shift (charge distribution) and bond distance (3J(H,H)) were considered. The results are consistent with charge delocalisation mainly in the C-5-C-9 and C-5'-C-9' regions and with bond inversion to retro shifted double bonds in the central C-13-C-13' region. A convention for denoting the charge delocalisation and bond types is presented. The experimental results are discussed relative to previous theoretical calculations of the beta,beta-carotene dication structure. (All-E) and (15-Z)-beta,beta-carotene provided the same dication. The NIR spectra and stability of dications prepared in the same manner from the related carotenes 20,20'-dinor-beta,beta-carotene, heptapreno-beta,beta-carotene and nonapreno-beta,beta-carotene were examined for comparison. Reactions of the beta,beta-carotene dication with selected nucleophiles provided products including isocryptoxanthin, isocarotene and mutatochrome with H2O as nucleophile, and isocryptoxanthin methyl ether, 8-methoxy-7,8-dihydro-beta,beta-carotene and isocarotene with CH3ONa as nucleophile. The formation of these products is rationalised from the structure assigned to the dication.     

Retro carotenoids with substituted 2,5-oxa-bicycloheptane end groups

BF₃-mediated formation of a 2,5-oxygen bridge from carotenoids with 2-hydroxy-β-type end groups accompanied by dehydrogenation and $\text{retro}$ shift of the polyene system is reported. The configuration of the Δ6,6′ double bonds are established by ¹H NMR.     

Carotenoids with two chromophores: carotenoid retinoates

In this study, carotenoid retinoates are described for the first time. The preparation was achieved by the azolide method. Various sec carotenols reacted with N-retinoylimidazol in the presence of catalytic amounts of sodium hydride. Mono- and diretinoates of (3R,3'R)-zeaxanthin and its (3S,3'S)-enantiomer, (9Z,9'Z; 3R,3'R)-alloxanthin, (3R,3'R)-7,8,7',8'-tetrahydro-3,3'-dihydroxy-β,β-carotene-8,8'-dione and (3R,6R,3'R,6'R)-ε,ε-carotene-3,3'-diol (lactucaxanthin), as well as monoretinoates of (3R,3'RS,6'R)-3'-methoxy-β,ε-caroten-3-ol, (3R,3'RS,6'R)-3-methoxy-β,ε-caroten-3'-ol, (2R,6'RS)-β,ε-caroten-2-ol, (3R,3'S; meso)-astaxanthin and (2'R)-aleuriaxanthin are reported in this study. Spectroscopic properties ((1)H-NMR mass spectrometry, visible and circular dichroism spectra) are discussed. Studies on other carotenoid derivatives with two chromophores are referred to here.     

Protonated canthaxanthins as models for blue carotenoproteins

It has been suggested that astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) in the carotenoprotein alpha-crustacyanin occurs in the diprotonated form. As a model system for protonated astaxanthin in [small alpha]-crustacyanin the reactions of canthaxanthin ([small beta],[small beta]-carotene-4,4[prime or minute]-dione) with Bronsted acids (CF(3)COOH and CF(3)SO(3)H) and the Lewis acid BF(3)-etherate have been investigated. Structures of C-5 protonated, C-7 protonated, enolised O-4 protonated and O-4,4[prime or minute], C-7 triprotonated canthaxanthin have been established by VIS-NIR and NMR spectroscopy. The charge distribution in the cations has been considered by comparison of the (13)C chemical shift difference relative to neutral relevant carotenoid models. The experimental evidence for protonated canthaxanthins differs significantly from previous AM1 calculations. Experimental data for O-4,4[prime or minute], C-7 triprotonated canthaxanthin relative to C-7 protonated canthaxanthin is considered a relevant model for O-4,4[prime or minute] diprotonated canthaxanthin, in comparison with neutral canthaxanthin. The positive charge was mainly located at C-6/6[prime or minute][dbl greater-than] C-8/8[prime or minute] > C-10/10[prime or minute] > C-12/12[prime or minute] > C-14/14[prime or minute][similar] C-15/15[prime or minute] in the polyene chain. Moreover, it was inferred that only 14% of the positive charge is delocalised to the polyene chain, the remaining charge must therefore be located at the protonated carbonyl moiety. The results are discussed in relation to previous solid state NMR studies of (13)C labelled astaxanthin in [small alpha]-crustacyanin and recent X-ray analysis of [small beta]-crustacyanin.     

Longer polyenyl cations in relation to soliton theory

The carotene-like polyenes decapreno-beta-carotene (C50), C54-beta-carotene (C54, first synthesis) and dodecapreno-beta-carotene (C60) with 15, 17 and 19 conjugated double bonds, respectively, were synthesized by double Wittig reactions. Introduction of a leaving group in allylic position failed, and cations were obtained by hydride elimination effected by i) triphenylcarbenium tetrafluoroborate-d15, prepared by a new method, or ii) treatment with trifluoroacetic acid-d. Deuterated reagents were employed for product analysis by 1H NMR. Parallel experiments were performed with beta,beta-carotene (C40). NIR spectra at room temperature and at -15 degrees C were employed for characterisation and stability studies of the cationic products. In CH2Cl2lambdamax in the 900-1350 nm region was recorded. NMR data for the cationic product of beta,beta-carotene obtained by the two new preparation methods were consistent with the two monocations previously characterised. The cationic products of the longer polyenes provided downfield-shifted, broadened signals, compatible with C50-monocation, mixed C54-mono- and dication and C60-dication. Combined NIR and NMR data suggest that the extent of charge delocalisation is limited by the maximum soliton width for cations obtained from linear polyenes with more than ca. 20 sp2-hybridized carbon atoms.     

Delocalized carotenoid cations in relation to the soliton model

A series of charge-delocalized carotenoid mono- and dications have been prepared by treatment of selected carotenoids with Br?nsted and Lewis acids. The detailed structures of the carbocations were established by NMR studies in the temperature range from -10 to -20 degrees C. The general strategy for structure elucidation by NMR of several cationic components in a mixture is outlined. Bond type and regions of bond inversion were established, as well as the charge distribution, which was determined from the difference in (13)C chemical shift at each carbon. This method gave a more accurate estimate for the partial charges than by using the Spiesecke-Schneider relationship. The resulting charge distribution was used as models for the structure of charged solitons. These carotenoid cations have the most delocalized charge so far determined, and the monocations represent the first experimental structure determination of positively charged solitons. The soliton width determined here is in good agreement with the results of previous AM1 calculations.     

Studies on the mechanism of the Carr-Price blue colour reaction

The reaction of retinoids (retinol, retinyl acetate and anhydroretinol) with Br?nsted acids was studied as a model system for the Carr-Price reaction. The anhydroretinylic cation was characterised by VIS and 2D NMR spectroscopy, including an estimate of the charge distribution and region of bond inversion, observed in a mixture of identified E/Z isomers. Products obtained by quenching with NaOMe-MeOH were identified by HPLC and MS. The classical Carr-Price reaction between retinol (vitamin A) and the Lewis acid SbCl(3) in saturated chloroform solution was reinvestigated by VIS, NMR, EPR, dynamic light scattering and chemical quenching. Whereas product instability and failure to provide informative NMR spectra indicated a radical cation, EPR results excluded free-radical species. Dynamic light scattering experiments, in comparison with model systems, revealed strong aggregation for the Carr-Price complex, rationalizing the low stability, NMR problems and dimerisation observed by chemical quenching. The VIS data support structural similarity of the blue Carr-Price product with the delocalized anhydroretinylic cation, and a detailed structure of the antimony complex is evaluated.     

Total syntheses of cross-conjugated carotenals

Total syntheses of the cross-conjugated carotenals renierapurpurin-20-al (χ,χ-caroten-20-al, 2), (2R,2' R)-tetradesoxybacterioruberin-20- al ((2R,2'R)-2,2'- bis-(3-methylbutyl)-3,4,3',4'-tetrahydro-ψ,ψ -caroten-20-al, 3) and (2R,6R,2'R, 6' R)-2,2'dimethyl-decapreno -?,? -caroten -25-al (4) from the common intermediate 8,8'-diapo-20-acetoxycarotene 8,8' dial (5) are described. The cross conjugated 20-(2,3 4-trimethylbenzal)renierapurpurin (16) has also been synthesized