Separation of (3R, 3′ R)-, (3R, 3′ S; meso)-, (3S, 3′ S)- Zeaxanthin, (3R, 3′ R, 6′ R)-, (3R, 3′ S, 6′ S)- and (3S, 3′ S, 6′ S)-Lutein via the dicarbamates of (S)-(+)-α-(1-naphthyl) ethyl isocyanate

A method is described for the qualitative and quantitative determination of configurational isomers of zeaxanthin (=3,3′ -dihydroxy-β, β -carotene) and lutein (=3,3′ -dihydroxy-α -cartotene). It is based on the reaction of these zeaxathin and lutein isomers with (S)-(+)-α-(1-naphthyl) ethyl isocyanate to afford diastereomeric dicarbamates, which are analyzed by HPLC.     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. IV. Neues Konzept für die Synthese von (3RS, 3′RS)-, (3S, 3′S)- und (3R, 3′R)-9,9′-dicis-7,8,7′,8′-Tetradehydroastaxanthin

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. IV. A Novel Concept for the Synthesis of (3RS, 3′RS)-, (3S, 3′S)- and (3R, 3′R)-9,9′-dicis-7,8,7′,8′-Tetradehydroastaxanthin Starting from readily available intermediates of the synthesis of astaxanthin, (3RS, 3′RS)-, (3R, 3′R)- and (3S, 3′S)-9,9′-di-cis-tetradehydroastaxanthin ( 1, 1a and 1b , resp.) were synthesized, 1 and 1b for the first time. Key features of this concept are: a) use of the unprotected, acetylenic phosphonium salts 8–12 , b) a two-step synthesis with 47% overall yield, and c) good chemical and optical purity of the end products.     

Temperaturabhängiger Circulardichroismus von (3S, 3′R)- und (3S, 3′ S)-Adonixanthin

The temperature dependent CD. spectra of (3S, 3′R)- and (3S, 3′S)-adonixanthin are compared with those of (3R, 3′R)-zeaxanthin ( 1 ) and (3S, 3′S)-astaxanthin ( 2 ). The room temperature spectra of 1 and 2 are quite similar. On cooling to ?180° the CD. of 1 simply intensifies, the CD. of 2 changes sign and becomes also very intense. The room-temperature CD. of (3S, 3′R)-adonixanthin ( 3 ) resembles closely those of 1 and 2 at room temperature. On cooling, however, it becomes weak and changes strongly its shape. With (3S, 3′S)-adonixanthin ( 4 ) it is the low-temperature spectrum which resembles that of 2 at low temperature, whereas the room-temperature spectrum is weak and quite different in shape. These observations can be explained with temperature dependent equilibria where the end groups are twisted out of the plain of the chain thereby conferring chirality to the conjugated system.     

Synthese der (3S,4R,3′S,4′R)- und (3S,4S,3′S,4′S)Crustaxanthine sowie weiterer Verbindungen mit 3,4-Dihydroxy-β-Endgruppen

Synthesis of (3S,4R,3′S,4′R)- and (3S,4S,3′S,4′S)-Crustaxanthins and Further Compounds with 3,4-Dihydroxy β-End-groups Starting from 3 , the enantiomerically pure title compounds were synthesized in eight steps. Spectra and HPLC systems are presented that allow a distinction between these isomers.     

C45- and C50-Carotenoids Part7 Total synthesis of (all-E,2R,6R,2′R,6′R)- and (all-E,2R,6S,2′R,6′S)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-γ,γ-carotene (sarcinaxanthin)

The synthesis of sarcinaxanthin ((2R,6R,2′R,6′R)- 1 ), a symmetrical C₅₀-carotenoid with two γ-end groups, isolated from Sarcina lutea and from Cellulomonas biazotea as major pigment, was based on the strategy C₂₀ + C₁₀ + C₂₀ = C₅₀ using camphoric acid as starting material for the C₂₀-end group 3. The key step of the synthesis is a ring enlargement of the cyclopentane derivative 10 with 2,4,4,6-tetrabromocyclohexa-2,5-dien-1-one (TBCO) to give the cyclohexane derivative 11 (Scheme 1). The spectroscopic data of the synthetic compound are in full agreement with the data of the isolated product and give the final proof for the (2R,6R,2′R,6′R) chirality of natural sarcinaxanthin.     

Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3,6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol), ein neues Carotinoid aus Paprika (Capsicum annuum)

Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3.6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene-5,5′-diol), a Novel Carotenoid from Red Paprika (Capsicum annuum) From red paprika (Capsicum annuum var. longum nigrum) cycloviolaxanthin was isolated as a minor carotenoid and, based on spectral data, assigned the symmetrical structure 8 .     

Stereochemische Korrelationen zwischen (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin und (–)-(R)-Linalol

Stereochemical Correlations between (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin and (–)-(R)-Linalol The optically active C₅- and C₄-building units 1 and 2 with their hydroxy group at a asymmetric C-atom were transformed to (–)-(1S,5R)-Frontalin ( 7 ) and (–)-(3R)-Linalol ( 8 ) respectively; 1 and 2 had been used earlier in the preparation of the chroman part of (2R,4′R,8′R)-α-Tocopherol ( 6a , vitamin E), and for introduction of the side chain in (25S,26)-Dihydroxycholecalciferol ((25S)- 4 ), a natural metabolite of Vitamin D₃. The stereochemical correlations resulting from these converions fit into a coherent picture with those correlations already known from literature and they confirm our earlier stereochemical assignments. A stereochemical assignment concerning the C(25)-epimers of 25,26-Dihydroxycholecalciferol that was in contrast to our findings and that initiated the conversion of 1 and 2 to 7 resp. 8 for additional stereochemical correlations has been corrected in the meantime by the authors [26].     

Isolation and Characterisation of (5R, 6S,5′R,8′R)- and (5R,6S,5′R,8′S)-Luteochrome from Brazilian Sweet Potatoes (Ipomoea batatas LAM.)

Luteochrome isolated from the tubers of a white-fleshed variety of sweet potato (Ipomoea batatas LAM .) has been shown by HPLC, ¹H-NMR and CD spectra to consist of a mixture of (5R,6S,5′R,8′R)- and (5R,6S,5′R,8′S)- 5,6:5′,8′-diepoxy-5,6,5′,8′-tetrahydro-β,β-carotene ( 1 and 2 , resp.). Therefore, its precursor is (5R,6S,5′R,6′S)-5,6:5′,6′-diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene ( 4 ). This is the first identification of luteochrome as a naturally occurring carotenoid and, at the same time, gives the first clue to the as yet unknown chirality of the widespread β,β-carotene diepoxide. These facts demonstrate that the enzymic epoxidation of the β-end group occurs from the α-side, irrespective of the presence of OH groups on the ring.     

Eine Suche nach 3′-Epilutein ( = (3R,3′S,6′R)-β,ε-Carotin-3,3′-diol) und 3′, O-Didehydrolutein (=(3R, 6′R)-3-Hydroxy-β,ε-carotin-3′-on) in Eigelb,in Blüten von Caltha palustris und in Herbstblättern

Search for the Presence in Egg Yolk, in Flowers of Caltha palustris and in Autumn Leaves of 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-Carotene-3,3′-diol) and 3′,O-Didehydrolutein ( =(3R,6′R)-3-Hydroxy-β,ε-carotene-3′-one) 3′.O-Didehydrolutein ( =(3R, 6′R)-3-hydroxy-β,ε-carotene-3′-one; 2) has been detected in egg yolk and in flowers of Caltha palustris. This is the first record for its occurrence in a plant. The compound shows a remarkable lability towards base; therefore, it may have been overlooked til now, because it is destroyed under the usual conditions of saponification of the carotenoid-esters. One of the many products formed from 2 with 1% KOH in methanol has been purified and identified as the diketone 3 ( =(3R)-3-hydroxy-4′, 12′-retro-β,β-carotene-3′,12′-dione). The identification of this transformation product from lutein might throw a new light on the metabolism of this important carotenoid in green plants. 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-carotene-3,3′-diol; 1) was not detected in egg yolk, but is present besides lutein in flowers of C. palustris, thus confirming an earlier report of the occurrence of an isomeric (possibly epimeric) lutein (‘calthaxanthin’) in that plant [21]. We were not able to detect even traces of 1 or 2 in the carotenoid fraction from autumn leaves of Prunus avium (cherry), Parrotia persica, Acer montanum (maple) and yellow needles of Larix europaea (larch). α-Cryptoxanthin (4) , a very rare carotenoid, was isolated in considerable quantity for the first time from flowers of C. palustris.     

Temperature and Concentration Dependent Circular Dichroism of Mono- and Di-cis Isomers of (3S,3′S)-Astaxanthin Diacetate

The circular dichroism (CD.) spectra of all-trans-(3S, 3′S) astaxanthin diacetate and its 9-cis, 13-cis, 9,9′-di-cis, 9,13′-di-cis, and 9,13-di-cis isomers conform to the rules previously formulated for optically active carotenoids with a 4-oxo-β-end ring containing an asymmetric C-atom [1]. Thus the CD. bands of the all-trans and the di-cis isomers show the same signs whereas those of the mono-cis isomers have opposite signs. The CD. spectra of all the astaxanthin diacetate isomers invert sign upon cooling to ?180°. The CD. spectra of the 9-mono-cis and 9,9′-di-cis isomers and to a lesser extent also those of the 9, 13′-di-cis and 9, 13-di-cis isomers are concentration dependent at ?180°, with the longest wavelength band giving at the higher concentration a bisignate CD. curve under the main absorption characteristic of aggregation. This phenomenon has been observed only in isomers with a 9-cis linkage. It is suggested that steric hindrance prevents such aggregation taking place in the other isomers.     

Confirmation of the Absolute (3R,3′S,6′R)‐Configuration of (all‐E)‐3′‐Epilutein

Circular dichroism (CD) spectroscopy was used to distinguish between the isomeric (all‐E)‐configured 3′‐epilutein ( 2 ) and 6′‐epilutein ( 8 ) to establish the absolute configuration of epilutein samples of different (natural and semisynthetic) origin, including samples of 2 obtained from thermally processed sorrel. Thus, the CD data of lutein ( 1 ) and epilutein samples ( 2 ) were compared. Our results unambiguously confirmed the (3R,3′S,6′R)‐configuration of all epilutein samples. Compound 2 was thoroughly characterized, and its ¹³C‐NMR data are published herewith for the first time.     

Carotinoide mit 7-Oxabicyclo[2.2.1]heptyl-Endgruppen. Teil I. Versuch einer Synthese von Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3,6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol)

Carotenoids with 7-Oxabicyclo[2,2.1]heptyl End Groups. Attempted Synthesis of Cycloviolaxanthin ( = (3S,5R,6S,3′S,5′R,6′R)-3,6:3′,6′- Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol) Starting from our recently described synthon (+)- 24 , the enantiomerically pure 3,6:4,5:3′,6′:4′,5′-tetraepoxy-4,5,4′,5′-tetrahydro-ε,ε-carotene ( 34 ) and its 15,15′-didehydro analogue 32 were synthesized in eleven and nine steps, respectively (Scheme 4). Chiroptical data show, in contrast to the parent ε,ε-carotene, a very weak interaction between the chiral centers at C(5), C(5′), C(6), C(6′), and the polyene system. Diisobutylaluminium hydride reduction of 32 lead rather than to the expected 15,15′-didehydro analogue 35 of Cycloviolaxanthin ( 8 ), to the polyenyne 36 (Scheme 5). We explain this reaction by an oxirane rearrangement leading to a cyclopropyl ether followed by a fragmentation to an aldehyd on the one side and an enol ether on the other (Scheme 6). This complex rearrangement includes a shift of the whole polyenyne chain from C(6), C(6′) to C(5), C(5′) of the original molecule.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VIII. Synthese von (3S,3′S)-7,8,7′,8′-Tetradehydroastaxanthin und (3S,3′S)-7,8-Didehydroastaxanthin (Asterinsäure)

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. VIII. Synthesis of (3S,3′S)-7,8,7′,8′-Tetradehydroastaxanthin and (3S,3′S)-7,8-Didehydroastaxanthin (Asterinic Acid) The synthesis of all-trans-(3S,3′S)-3,3′-dihydroxy-7,8, 7′,8′-tetradehydro-β, β-carotene-4,4′-dione ( 1 ), of all-trans-(3S,3′S)-3,3′-dihydroxy-7, 8-didehydro-β,β-carotene-4,4′-dione ( 2 ) (asterinic acid = mixture of 1 and 2 ), and of their 9,9′-di-cis- and 9-cis-isomers is reported starting from (4′S)(2E)-5-(4′-hydroxy-2′, 6′,6′-trimethyl-3′-oxo-l′-cyclohexenyl)-3-methyl-2-penten-4-ynal ( 8 ). The absolute configuration (3S,3′S) for both components 1 and 2 of asterinic acid ex Asterias rubens is confirmed on the basis of spectroscopic and direct comparison.     

C45- and C50-Carotehoids. Part 8. Synthesis of (all-E,2S,2′S)-bacterioruberin, (all-E,2S,2′S)-monoanhydrobacterioruberin, (all-E,2S,2′S)-bisanhydrobacterioruberin, (all- E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydro- bacterioruberin,and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin

Starting from (R)-3-hydroxybutyric acid ((R)- 10 ) the C₄₅- and C₅₀-carotenoids (all-E,2S,2′S)-bacterioruberm ( 1 ), (all-E,2S,2′S)-monoanhydrobacterioruberin ( 2 ), (all-E,2S,2′S)-bisanhydrobacterioruberin ( 3 ), (all-E,2R,2′R)-3,4,3′,4′-tetrahydrobisanhydrobacterioruberin ( 5 ), and (all-E,S)-2-isopentenyl-3,4-dehydrorhodopin ( 6 ) were synthesized. By comparison of the chiroptical data of the natural and the synthetic compounds, the (2S)- and (2′S)-configuration of the natural products 1–3 and 6 was established.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. II. Synthese von (3 S, 3′S)-Astaxanthin

Synthesis of optically active natural carotenoids and structurally related compounds. II. Synthesis of (3S, 3′S)-astaxanthin The syntheses of rac. astaxanthin, (3 S, 3′S)-astaxanthin ( 1 ), its 15-cis isomer ( 21 ), its diacetate ( 22 ), and of (3 S, 3′ S)-15, 15′-didehydroastaxanthin ( 20 ) are reported.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. V. Synthese von (3R, 3′R)-, (3S, 3′S)- und (3R,3′S; meso)-Zeaxanthin durch asymmetrische Hydroborierung. Ein neuer Zugang zu Optisch aktiven Carotinoidbausteinen. Vorläufige Mitteilung

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. V. Synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin by Asymmetric Hydroboration. A New Approach to Optically Active Carotenoid Building Units The synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin ( 1 ), ( 19 ) and ( 21 ) is reported utilizing asymmetric hydroboration as the key reaction. Thus, safranol isopropenylmethylether ( 4 ) is hydroborated with (+)- and (?)-(IPC)₂BH to give the optically pure key intermediates 5 and 7 resp., which are transformed into the above-mentioned C₄₀-compounds.     

Carotinoide mit 7-Oxabicyclo[2.2.1]heptyl-Endgruppen. Teil II. Synthese von (2S,5R,6S,2′S,5′R,6′S)-2,5:2′5′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin

Carotenoids mit 7-Oxabicyclo[2.2.1]heptyl-End Groups. Synthesis of (2S,5R,6S,2′S,5′R,6′S)-2,5:2′5′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene Mukayama's ester 6 (methyl (1S,2R,5S)-2,5-epoxy-2,6,6-trimethylcyclohexane-1-carboxylate) was transformed in a few conventional steps into the title compound 14 . Its CD curve was found to be significantly different from that of the analogous 3,6-epoxide, a fact we tentatively lake as an indication of a (weak) electronic interaction between the ring O-atom and the π-orbitals of the polyene chain.     

3′-(1,2,3-Triazol-1-yl)-2′,3′-dideoxythymidine and 3′-(1,2,3-triazol-1-yl)-2′,3′-dideoxyuridine

Cycloaddition of different acetylenic compounds on the azido function of 3′-azido-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxyuridine afforded products with a 1,2,3-triazol-1-yl substituent in the 3′-position. In contrast with the parent compounds, these triazolyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).