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Antioxidative-activity-guided fractionation of extracts of the aerial parts of the title plant yielded the two novel abietanoid diterpenoids 11,20-dihydroxysugiol (=11,12,20-trihydroxyabieta-8,11,13-trien-7-one; 3) and 1,11-epoxy-6,12-dihydroxy-20-norabieta-1(10),5,8,11,13-pentaen-7-one (4) in addition to 11-hydroxysugiol (=12-O-demethylcryptojaponol=11,12-dihydroxyabieta-8,11,13-trien-7-one; 2) and the main constituent carnosolon (=6,20-epoxy-6,11,12-trihydroxyabieta-8,11,13-trien-7-one; 1). The structures were established on the basis of spectroscopic, chiroptic, and X-ray crystallographic evidence.

A series of new esters of lutein (1a) have been prepared with the aim of confirming the structure of lutein via an X-ray crystal-structure analysis. Although well crystallized, only one of the derivatives, the (−)-(1R)-menthyl carbonate (1i) proved to be useful for a complete structure analysis. The same derivative of zeaxanthin (2a) also allowed its crystal structure to be determined. Both analyses represent the first successful X-ray crystal structure analyses of the most important xanthophylls. At the same time, they confirm both the constitution and absolute configuration of 1a and 2a that had been deduced earlier by classical methods.

Incubation of deuteriated precursors in cultures of Flavobacterium produced specifically deuteriated carotenoids. Analysis of these led to several conclusions: i) Lycopene is a direct precursor of β,β-carotene. ii) Its terminal Me groups retain their integrity during cyclization: there is a stereospecific folding of the 1,5-diene. The Me(16,16′) groups of lycopene become the Me(16,16′) of β,β-carotene. Consequently, the folding must follow the C2(E,E) mode. iii) Incorporation of deuterium was sufficiently extensive to permit CD measurements on the isolated β,β-carotene, allowing its centers of chirality to be assigned as (1S,1′S). iv) The same chirality resulted from incorporation of [2H3]mevalonate into zeaxanthin. The syntheses of specifically deuteriated [2H3]GPP, [2H3]FPP, and [2H3]GG are described.

(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 ϵ-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 OHC(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.

Synthesis of (6R, all-E)-Neoxanthin and Related Allenic Carotenoids We present the first synthesis of enantiomerically pure neoxanthin (1) by a Wittig-Horner condensation between the ylide from the novel diethyl 12′-apo-15, 15′-didehydroviolaxanthin-12′-phosphonate (35) and the allenic C15-aldehyde 31 (Scheme 4) via the crystalline 15, 15′-didehydroneoxanthin (36; 70% yield). After partial hydrogenation of the triple bond of 36 and isomerisation of the (15Z)-intermediate 37, neoxanthin (1) was obtained in good yield. Similar syntheses gave (15Z, 9′Z)-neoxanthin (45; Scheme 5) and (9Z)-15, 15′-didehydroneoxanthin (47; Scheme 6). Comparison of the physical data of synthetic 1 with those of a freshly isolated sample of neoxanthin from the flowers of Trollius europaeus confirmed their identity. The unusually low melting point of 1 is caused by a very easy thermal isomerisation into a mixture of the neochromes 4 and 5 (Scheme 1). Such a thermal rearrangement is not observed with 15, 15′-didehydroneoxanthin (36). To explain this, we assume a zwitterionic excited state of the allenic group that induces the rearrangement of the violaxanthin end group into the furanoid epoxide (Scheme 7).

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.

Synthesis of Enantiomerically Pure Mimulaxanthin and of Its (9Z,9′Z)- and (15Z)Isomers We present the details of a synthesis of optically active, enantiomerically pure stereoisomers of mimulaxanthin (=(3s,5R,6R,3′S,5′R,6′R)-6,7,6′,7′-tetradehydro-5,6,5′,6′-tetrahydro-β,β-carotin-3,5,3′,5′-tetrol) either as free alcohols 1a and 24a or as their crystalline (t-Bu)Me2Si ethers 1b and 24b. Grasshopper ketone 2a, a presumed synthon, unexpectedly showed a very sluggish reaction with Wittig-Horner reagents. Upon heating with the ylide of ester phosphonates, an addition across the allenic bond occurred. On the contrary, a slow but normal 1,2-addition took place with the ylide from (cyanomethyl)phosphonate but, unexpectedly, with concomitant inversion at the chiral axis. So a mixture of(6R,6S,9E,9Z)-isomers 6–9 was produced {(Scheme 1). However, a fast and very clean 1,2-addition occurred with the ethynyl ketone 12 to yield the esters 13 and 14 (Scheme 2). DIBAH reduction of the separated stereoisomers gave the allenic alcohols 15 and 16 in high yield. Mild oxidation to the aldehydes 17 and 18 followed by their condensation with the acetylenic C10-bis-ylide 19 led to the stereoisomeric 15,15′-didehydromimulaxanthins 20 and 22, respectively (Schemes 3 and 4). Mimulaxanthins 1 and 24 were prepared by partial hydrogenation of 20 and 22 followed by a thermal (Z/E)-isomerization. As expected, the mimulaxanthins exhibit very weak CD curves, obviously caused by the allenic bond that insulates the chiral centers in the end group from the chromophor. On the contrary, some of the C15-allenic synthons showed not only fairly strong CD effects but also a split CD curve which, in our interpretation, results from an exciton coupling between the allene and the C(9)C(10) bond. We postulate a rotation around the C(8)C(9) bond, presumably caused by an intramolecular H-bond in 16 or by a dipol interaction between the polarized double bonds in 6, 7, 8, and 17.

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.

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-e,e-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 e,e-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.

Neoflor and 6-Epineoflor from Flowers of Trollius europaeus; Highfield 1H-NMR Spectra of (all-E)-Neoxanthin and (9′Z)-Neoxanthin Re-isolation of the very polar carotenoids from flowers of the title plant furnished two epimeric pentahydroxy compounds. Based on spectroscopical and chiroptical arguments and by chemical correlation with neoxanthin, their structures were established as 11 (proposed name neoflor) and 12 (6-epineoflor), Decoupling experiments and COSY-2D-1H-NMR spectra allowed a complete assignement of the vinyl protons of the two isomers, and furthermore, for the first time, also of those of (all-E)-neoxanthin and (9′Z)-neoxanthin.

A Further, Now Successful Search for 3′-Epilutein in Plants The 3′-epilutein, an extremely rare carotenoid, found till now in only one plant, was detected in anthers of flowers of several roses and in those of peonies.

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.

Synthesis of Optically Pure Grasshopper Ketone and of Its Diastereoisomers and Related Compounds Starting from our previously described synthon 1, the synthesis of four enantiomerically pure grasshopper ketons (diastereoisomeric 4-(2′,4′-dihydroxy-2′,6′,6′-trimethylcyclohexylidene)but-3-en-2-ons) and of their oxo derivatives was performed. Spectral and chiroptical data are presented.

Structure of the Valenciaxanthins and Valenciachromes Valenciaxanthin, a carotenoid first isolated from Californian Valencia orange juice in 1952/1954 by American scientists, was re-isolated from fresh Spanish ‘Navelinas’ and shown, by spectroscopical and chiroptical examination, to have the unexpected (9Z)-10′-apo-11′,12′-dihydroviolaxantin-10′-ol structure 6. A further, very minor component represents the (all-E)-structure 7. Therefore, the Valenciachromes are the furanoid rearrangement products of 6 and 7 and, thus, stereoisomers of the 10′-apo-11′,12′-dihydroauroxanthiiv 10′-ols 8. Valenciaxanthin represents a modification of the common cleavage of carotenoids in higher plants according to the scheme C40 C27 + C13, insofar as the reduction step not only includes the aldehyde function but also the subsequent conjugated double bond.

Synthesis of Plectranthons, Diterpenoid Phenanthrene-1,4-diones The following phenanthrene-1,4-diones have been synthesized by using the photocyclization of the corresponding highly substituted stilbenes as the key step: 3-hydroxy-5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione (1), (RS)-, (R)-, and (S)-2-[3-hydroxy-5,7,8-trimethyl-1,4-dioxophenanthren-2-yl]-1-methylethyl acetate (2, 31, and 32, resp.), 3-hydroxy-7,8-dimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione (3), 3-hydroxy-7,8,10-tri-methyl-2-(prop-2-enyl)phenanthrene-1,4-dione (4), 5,7,8-trimethyl-2-(prop-2-enyl)phenanthrene-1,4-dione (17), and 3-hydroxy-2-methylphenanthrene-1,4-dione (42). The quinones 1 and 3 proved to be identical with the recently isolated plectranthons A and C. Compounds 2, 31, and 32 exhibited the same UV/VIS, IR, 1H-NMR and mass spectra as natural plectranthon B, but had different melting points. This might be due either to crystal modifications or to diastereoisomerism caused by the helical structure of the phenanthrene-1,4-dione skeleton. The spectral data of synthetic 4 were not compatible with those of natural plectranthon D for which structure 4 had been proposed based mainly on 1H-NMR arguments concerning the chemical shifts of HC(9) and HC(10) in 1–3. Extensive 1H-NMR investigations have now revealed that the currently stated assignments of the HC(9)/ HC(10) AB system have to be reversed for highly substituted phenanthrene-1,4-diones: in the model compounds 2-methylphenanthrene-1,4-dione (41) and 2, HC(10) resonates al lower field as expected (peri-position), whereas in the highly substituted congeners 1, 2, 3, 31, and 32, HC(9) is shifted paramagnetically, a fact which had lead to the erroneous assignment of structure 4 for natural plectranthon D.

Leaf-gland Pigments: Coleons S and T from Plectranthus caninus ROTH(Labiatae), New Hydroquinones of the Abietane Series with a Diosphenol/trans-A/B-6,7-Diketone Structure. Coleons S and T were isolated from the more polar fractions from extracts of the above mentioned plant. Coleon S, C20H26O6, has been shown to have structure 1a, and coleon T, C20H26O6, structure 2.

Synthesis of (-)-(R)-4-Hydroxy-β-ionone and (-)-(5 R, 6 S)-5-Hydroxy-4,5-dihydro-α-ionone aus (-)-(S)-α-Ionone The absolute configuration of the chiral 4-hydroxy-β-ionones and 5-hydroxy-4,5-dihydro-α-ionones has been determined by chemical connection with (-)-(S)-α-ionone i.e. by stereoselective epoxidation of the latter, followed by base catalyzed opening of the epoxide as well as by its hydride reduction.

Partial Syntheses and Reactions of Abietanoid Derivatives (Lanugones) from Plectranthus lanuginosus and of Related Compounds Interconversions by partial syntheses of several lanugones establish their absolute configuration at C(15). Unexpected reactions exemplify the unique reactivity of these abietanoic diterpenes, - Lanugone O (4) was prepared in several steps from (15S)-coleon C (8a; Scheme 2) thus establishing its (15S)-configuration. One of the intermediates, the 12-O-acetyl-6-oxoroyleanone 12, through acetyl-migration sets up an equilibrium with the vinylogous quinone 13 (Scheme 3). - The chirality at C(15) in the dihydrofuran moiety of lanugone Q (16) was proven by acid-catalyzed conversion of lanugone O (4) to 16. - Instead of the usual nucleophilic attack shown by quinomethanes, lanugone L (1) is electrophilically substituted at C(7) by acetic anhydride/pyridine (Scheme 1). - In a homosigmatropic [1,5]-H-shift, lanugone G (17) in solution is converted to the corresponding allyl substituted royleanone 18 (Scheme 4). - Methanolysis of lanugone J (19) leads to the expected royleanone 20 having the 2-methoxypropyl side chain (Scheme 5). Similar reactions were found in acetolytic reactions. However, treatment-of spirocoleons with SOCl2/DMF produces mainly 12-deoxyroyleanones with allyl- and 2-chloropropyl groups, i. e. 1926 and 27; 28 29. The possible natural occurrence of these compounds is emphasized.

Activated Quinones: Regiospecific Syntheses of Substituted Dibenzo [b, d]pyran-6-ones and Benzo[b]naphtho [d]pyran-6-ones The reaction of 2-methoxycarbonyl-1, 4-benzoquinone (1) with substituted phenols leads in an acid-catalyzed, regiospecific way to substituted dibenzo [b, d]-pyran-6-ones (compounds 3 and 6). The cycloaddition of 1,3-butadiene to the latter yields compounds 7. Tautomerisation of 7 and oxidation gives the benzo[b]-naphtho[d]pyran-6-ones 8 and 10, respectively.

Synthesis of Enantiomerically Pure Apoviolaxanthinoic Acids, Apoviolaxanthinols, and Apoviolaxanthinals (Including Persicaxanthin, Sinensiaxanthin, and β-Citraurin Epoxide) and of their Furanoid Rearrangement Products Starting from (1′S,2′R,4′S,2E,4E)-5-(1′,2′-epoxy-4′-hydroxy-2′,6′,6′-trimethylcyclohexy1)-3-methy1-2,4-pentadienal (3), a recently described synthon [6], a full range of C20-, C25-, C27-, and C30-polyenic acids, alcohols, and aldehydes and their (8R)- and (8S)-diastereoisomeric furanoid rearrangement products was prepared. The synthetic C25-alcohols proved to be identical with persicaxanthin (= 12′-apoviolaxanthin-12′-ol) and perisicachromes (= 12′-apoauroxanthin-12′-ols) and the C27-alcohols analogously with sinensiaxanthin and sinensiachromes. A correlation between the sign of the Cotton effects in the CD spectra of 5,6-and 5,8-epoxides and their configuration at C(6) and C(8), respectively, was established.

The Diastereomeric Aurochromes: Their Synthesis, Analysis and Chiroptical Properties (all-E)-Aurochrome (5,8:5′,8′-diepoxy-5,8,5′,8′-tetrahydro-β,β-carotene; 1) has two pairs of constitutionally identical chiral centres and, therefore, is expected to exist in four pairs of enantiomers and two meso-forms. Using starting materials with well-defined configuration, we performed the syntheses of the following pure aurochromes: (5R,8R,5′R,8′R)-aurochrome (2) and its racemate, Meso-(5R,8R,5′S,8′S)-aurochrome (3), (5 R,8 S,5′ R,8′ S)-aurochrome (4) and its racemate, meso-(5R,8S,5′S,8′R)-aurochrome (5), (5R,8R,5′R,8′S)-aurochrome (6) and its racemate. The (5RS,8RS,5′SR,8′RS)-aurochrome (7) was detected chromatographically, using a HPLC system that allows clean separation of the four racemic- (or optically active) and the two meso-aurochromes. The optically active autochromes 2 and 4 exhibit non-conservative CD spectra with strong Cotton effects of opposite but not mirror-like tracings. Solutions of aurochromes in CHCl3, in the presence of HCl, undergo epimerization at C(8). Those epimers with CH3trans to C(9) slightly predominate under equilibrium conditions. Deprotonation of the phosphonate (±)-14 with strong base causes isomerization at the terminal oxirane into a dihydrofuran. This reaction allowed convenient syntheses of the diastereoisomeric aurochromes (±)-2, 3, (±)-4, 5, (±)-6, and (±)-7 and of (5RS, 8RS)- and (5RS, 8SR)-12′-apo-aurochrome-12′-als (21 and 22, respectively).

Structure and properties of 5-epi-flavoxanthin and 5-epi-chrysanthemaxanthin The absolute configurations of 5-epi-flavoxanthin (6) and 5-epi-chrysanthemaxanthin (7) prepared by acid catalysed rearrangement of semi-synthetic lutein epoxide 5 are shown to be (3S, 5S, 8R, 3′R, 6′R) and (3S, 5S, 8S, 3′R, 6′R), respectively. Contrary to published data [5] the relationship of the polyene chain and H3(18) on the dihydrofurane ring is cis for the pair of stereoisomers having a Δδ = δ (HC(7)) − δ (HC(8)) = 0,22 ppm and 3J ≡ 0. These conclusions are in full accord with the chiroptical data.

Carotenoids from Hips of Rosa pomifera: Discovery of (5Z)-Neurosporene; Synthesis of (3R, 15Z)-Rubixanthin Extensive chromatographic separations of the mixture of carotenoids from ripe hips of R. pomifera have led to the identification of 43 individual compounds, namely (Scheme 2): (15 Z)-phytoene (1), (15 Z)-phytofluene (2), all-(E)-phytofluene (2a), ξ-carotene (3), two mono-(Z)-ξ-carotenes (3a and 3b), (6 R)-ϵ, ψ-carotene (4), a mono-(Z)-ϵ, ψ-carotene (4a), β, ψ-carotene (5), a mono-(Z)-β, ψ-carotene (5a), neurosporene (6), (5 Z)-neurosporene (6a), a mono-(Z)-neurosporene (6b), lycopene (7), five (Z)-lycopenes (7a–7e), β, β-carotene (8), two mono-(Z)-β, β-carotenes (probably (9 Z)-β, β-carotene (8a) and (13 Z)-β, β-carotene (8b)), β-cryptoxanthin (9), three (Z)-β-cryptoxanthins (9a–9c), rubixanthin (10), (5′ Z)-rubixanthin (=gazaniaxanthin; 10a), (9′ Z)-rubixanthin (10b), (13′ Z)- and (13 Z)-rubixanthin (10c and 10d, resp.), (5′ Z, 13′ Z)- or (5′ Z, 13 Z)-rubixanthin (10e), lutein (11), zeaxanthin (12), (13 Z)-zeaxanthin (12b), a mono-(Z)-zeaxanthin (probably (9 Z)-zeaxanthin (12a)), (8 R)-mutatoxanthin (13), (8 S)-mutatoxanthin (14), neoxanthin (15), (8′ R)-neochrome (16), (8′ S)-neochrome (17), a tetrahydroxycarotenoid (18?), a tetrahydroxy-epoxy-carotenoid (19?), and a trihydroxycarotenoid of unknown structure. Rubixanthin (10) and (5′ Z)-rubixanthin (10a) can easily be distinguished by HPLC. separation and CD. spectra at low temperature. The synthesis of (3 R, 15 Z)-rubixanthin (29) is described. The isolation of (5 Z)-neurosporene (6a) supports the hypothesis that the ϵ-end group arises by enzymatic cyclization of precursors having a (5 Z)- or (5′ Z)-configuration.

Two Optically Active Luteochromes: Preparation, Spectra and Chiroptical and Chromatographic Properties Selective rearrangement of (5R,6S,5′ R,6′S)-5,6:5′, 6′ -diepoxy-5,6,5′, 6′ -tetrahydro- β,β -carotene with the aid ofan ethereal solution of malonic acid leads to the mixture of the C(8′)-epimeric luteochromes. HPLC separation gave the pure isomers. This is the first report on th preparation of optically active luteochromes.

Isolation and Structure Elucidation of 36 Diterpenoids from Leaf-Glands of Plectranthus edulis (VATKE) T.T. AYE Analysis of the polar diterpenoids from the yellow glands of the title plant from Kenya and Abyssinia led to the identification of several novel abietanoids. Main compound is the known edulon A (40), a 5(43) abeo-abietane. Minor compounds include 6 different royleanones, 15 spirocoleons, 3 vinylogous quinones, 8 acylhydroquinones (as their 6,7-dioxo compounds or the tautomeric disophenols), 2 naphthaquinones (as the 1,10-seco-abietanoids), and deacetyledulon A. The known coleon-A-lactone (37) now has also been found in Plectranthus edulis. The intermediacy of the γ-enollactol 44, combined with a leaving group on C(3) is postulted to explain the biogenesis of the unusual 4H-5-oxaaceanthrylen skeleton of edulon A.

Leaf-gland Pigments: 6-Novel p-Quinomethanes of the Abietane Series from Plectranthus parviflorus WILLD The above mentioned plant accumulates in its red coloured leaf-glands a complex mixture of strongly dehydrogenated abietanols. They were separated (with difficulties) to yield 6 novel compounds. Spectroscopic and chiroptic data show them to be esters of either 11, 19-dihydroxy- or 2 α, 11-dihydroxy-abieta-5, 7, 9 (11), 13-tetraen-12-one 2a and 3a, respectively. Specifically, the 19-O-p-hydroxybenzoate (2d) parvifloron C, the 19-O-vanilloate (2c) parvifloron B, the 19-O-p-hydroxy-benzoate (2d) parvifloron C, the 19-O-3′,4′-dihydroxybenzoate (2e) parvifloron E, the 2 α-O-p-hydroxybenzoate (3b) parvifloron D, and the 2 α-O-3′,4′-dihydroxy-benzoate (3c) parvifloron F. Reduction by LiAlH4 splits the ester function and reduces the p-quinomethane to a colourless pyrocatechol derivative which, by air oxidation, regenerates the red p-quinomethane system of 2a and 3a.

Horminone, taxoquinone and other royleanones, obtained from two Abyssinian Plectranthus species (Labiatae). From the coloured glands on the leaves of two botanically unclassified Plectranthus sp. from Abyssinia, a series of royleanones has been isolated, namely royleanone (1) and 6,7-dehydroroyleanone (2) from one species, and 6,7-dehydroroyleanone, horminone (3), taxoquinone (4), 6β, 7α-dihydroxyroyleanone (5), 7α-acetoxy-6β-hydroxyroyleanone (6) and 7-oxoroyleanone (7) respectively, from the other.

Synthesis of [16,16,16,16′,16′,16′ 2H6]Lycopene Lycopene having at both ends the deuteriated methyl groups trans to the chain has been synthesized for further biochemical experiments aimed to elucidate the stereochemistry of the cyclization step. Incidentally a gas-chromatographic separation of the isotopisomers 1 and 2g has been observed.

Activated quinones: substitution reactions by methoxy-carbonyl-1,4-benzoquinone of azulenes, benzofuran and indoles; regiospecific syntheses of polymethoxy-fluorenones; a new synthesis of the 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one system. We present new electrophilic substitution reactions of azulenes and 5-membered heterocyclics by methoxy-carbonyl-1,4-benzoquinone. Hydroquinones 3a and 5 are prepared from azulene, and 3b from guaiazulene (see Scheme 1). Benzofuran undergoes α- and β-substitution (hydroquinones 910) (see Scheme 2). Only β-substitution is observed with indole (hydroquinone 20) (see Scheme 4). After methylation, saponification and intramolecular acylation of the substituted indoles 22c, 22d, derivatives of 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one have been obtained. Spectral data prove the presence of the methylidenequinone tautomer. By protonation or alkylation at the carbonyl group of 23, the violet, highly delocalized 16π-electron systems 25 are generated. Analogously, polymethoxy-fluorenones have been prepared from methoxylated diphenylquinones 15 (see Scheme 3). They also are transformed by protonation and alkylation to the highly coloured and delocalized 12 π-electron systems 18. By contrast, anthracene is not substituted by methoxycarbonyl-1,4-benzoquinone, but undergoes cycloaddition to the triptycene derivative 1 (see Scheme 1). A summary is presented of previously described reactions of activated quinones.

Partial Synthesis of Grandidones A, 7-Epi-A, B, 7-Epi-B, C, D and 7-Epi-D, from 14-Hydroxytaxodione Oxydative addition of coleon U (6) to 14-hydroxytaxodione (5) in the presence of Fetizon's reagent mainly leads to grandidone A (1a) and 7-epigrandidone A (1b) (ca. 15:1), whereas coleon V (7) and 5 under the same conditions yield grandidone B (2a) and 7-epigrandidone B (2b) (ca. 3:1). Dimerization of 14-hydroxytaxodione (5) gives grandidone C (3; ca. 40%), grandidone D (4a; ca. 50%) and 7-epigrandidone D (4b; ca. 10%). All these compounds obtained by partial synthesis are in every respect identical with the natural products, thus establishing their absolute configurations. The thermal transformation of grandidone C (3) to grandidone D (4a)/7-epigrandidone D (4b) and interconversions of 4a and 4b were achieved. Oxydative addition of coleon U (6) to 14-hydroxytaxodione (5) in the presence of Fetizon's reagent mainly leads to grandidone A (1a) and 7-epigrandidone A (1b) (ca. 15:1), whereas coleon V (7) and 5 under the same conditions yield grandidone B (2a) and 7-epigrandidone B (2b) (ca. 3:1). Dimerization of 14-hydroxytaxodione (5) gives grandidone C (3; ca. 40%), grandidone D (4a; ca. 50%) and 7-epigrandidone D (4b; ca. 10%). All these compounds obtained by partial synthesis are in every respect identical with the natural products, thus establishing their absolute configurations. The thermal transformation of grandidone C (3) to grandidone D (4a)/7-epigrandidone D (4b) and interconversions of 4a and 4b were achieved. Oxydative addition of coleon U (6) to 14-hydroxytaxodione (5) in the presence of Fetizon's reagent mainly leads to grandidone A (1a) and 7-epigrandidone A (1b) (ca. 15:1), whereas coleon V (7) and 5 under the same conditions yield grandidone B (2a) and 7-epigrandidone B (2b) (ca. 3:1). Dimerization of 14-hydroxytaxodione (5) gives grandidone C (3; ca. 40%), grandidone D (4a; ca. 50%) and 7-epigrandidone D (4b; ca. 10%). All these compounds obtained by partial synthesis are in every respect identical with the natural products, thus establishing their absolute configurations. The thermal transformation of grandidone C (3) to grandidone D (4a)/7-epigrandidone D (4b) and interconversions of 4a and 4b were achieved. Oxydative addition of coleon U (6) to 14-hydroxytaxodione (5) in the presence of Fetizon's reagent mainly leads to grandidone A (1a) and 7-epigrandidone A (1b) (ca. 15:1), whereas coleon V (7) and 5 under the same conditions yield grandidone B (2a) and 7-epigrandidone B (2b) (ca. 3:1). Dimerization of 14-hydroxytaxodione (5) gives grandidone C (3; ca. 40%), grandidone D (4a; ca. 50%) and 7-epigrandidone D (4b; ca. 10%). All these compounds obtained by partial synthesis are in every respect identical with the natural products, thus establishing their absolute configurations. The thermal transformation of grandidone C (3) to grandidone D (4a)/7-epigrandidone D (4b) and interconversions of 4a and 4b were achieved.

Diazo coupling of 3,4-dimethoxyfuran with aryl diazonium ions 3,4-Dimethoxyfuran (1) easily reacts with aryl diazonium chloride in aqueous pyridine in an expected 1, 4-addition reaction. From the isolable primary addition product pyridine is displaced by alcohols, phenols or thiols to yield 4-alkoxy- or 4-phenoxy- or 4-thiophenoxy-derivatives of 2,3-dimethoxy-2-buten-4-olide (3). Attempts to convert them into azo compounds by a base catalysed 1, 6-elimination reaction failed. Oxidation of 3a and 3c with DDQ results in the formation of the mono p-nitrophenylhydrazone of 3, 4-dimethoxymaleic acid anhydride. On the other hand, the thiophenoxy compound 3g is smoothly converted by MnO2 into the authentic furan-2-azobenzene derivative 5.

Absolute Configuration of Loroxanthin (=(3R, 3′R, 6′R)-β, ϵ-Carotene-3, 19, 3′-triol) ‘Loroxanthin’, isolated from Chlorella vulgaris, was separated by HPLC. methods in two major isomers, a mono-cis-loroxanthin and the all-trans-form. Solutions of the pure isomers easily set up again a mixture of the cis/trans-isomers. Extensive 1H-NMR. spectral measurements at 400 MHz allowed to establish the 3′, 6′-trans-configuration at the ϵ-end group in both isomers and the (9E)-configuration in the mono-cis-isomer. The absolute configurations at C(3) and C(6′) were deduced from CD. correlations with synthetic (9Z, 3R, 6′R)-β, ϵ-carotene-3, 19-diol (5) and (9E, 3R, 6′R)-β, ϵ-carotene-3, 19-diol (6), respectively. Thus, all-trans-loroxanthin (3) is (9Z, 3R, 3′R, 6′R)-β, ϵ-carotene-3, 19, 3′-triol and its predominant mono-cis-isomer is (9E, 3R, 3′R, 6′R)-β, ϵ-carotene-3, 19, 3′-triol (4). Cooccurrence in the same organism and identical chirality at all centers suggest that loroxanthin is biosynthesized from lutein (2).

A novel carbohydrate has previously been isolated from human bile as a complex glycoside of bilirubin [1]. This compound has been tentatively identified as 3-C-hydroxymethyl-D-riburonic acid. To test this structural assignment the proposed branched-chain uronic acid was synthesized. Gas chromatographic and mass spectrometric comparison of the natural and synthetic materials indicated that the proposed structure, 3-C-hydroxymethyl-D-riburonic acid, did not apply to thc natural product.

Structure Determination of Azafrin Methyl Ester 5-O-Monomethyl Ether by 13C-NMR.-Specta. The structure of the monomethyl ether (2) of azafrin methyl ester (1) was determined by a partial analysis of the 13C-NMR.-spectra. Assignments of quaternary carbon atoms and methyl groups in the cyclohexane ring were achieved using vicinal 13C-, 1H-spin coupling. Substituent effects on methyl and methylene carbon atoms in 2 are discussed with respect to the conformation of the methoxy group. The spectra prove C(5)OH as the site of methylation. Therefore C(5)OH is less hindered than C(6)OH.

Diastereoisomeric Mutatochromes: Separation, Absolute Configuration, and Spectra and Chromatographic Behaviour (5S, 6R)-5, 6-Epoxy-5, 6-dihydro-β, β-carotent (2), prepared from azafrinal (1) was rearranged in an acid-catalyzed reaction into the mixture of (5S, 8S)- and (5S, 8 R)-5, 8-epox-5, 8-dihydro-β, β-carotenes = ‘mutatochrome’. HPLC separation of the individual diastereoisomers led to the pure isomers for the first time. Their structures were assigned by analysis of the characteristic pattern of the signals of HC(7) and HC(8), respectively, in 1H-NMR spectra. Although many reports of the occurrence of ‘mutatochrome’ exist, it is as yet not clear whether optically active or racemic forms predominate in nature. Combination of HPLC separations with UV/VIS and CD spectra should now allow an unambigous identification of the isomer in question.

Separation and Absolute Configuration of the C(8)-Epimeric (app-E)-Neochromes (Trollichromes) and -Dinochromes The C(8′)-epimers of (all-E)-neochrome were separated by HPLC and carefully characterized. The faster eluted isomer, m.p. 197.8–198.3°, is shown to have structure 3 ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-dodehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). To the other isomer, m.p. 195-195.5°, we assign structure 6, ((3S,5R,6R,3′S,5′R,8′R)-5′,8′-epoxy-6,7-didehydro-5,6,5′,8′-tetrahydro-β,β-carotene-3,5,3′-triol). The already known epimeric dinochromes (= 3-O-acetylneochromes) can now be formulated as 4 and 5, (‘epimer 1’ and its trimethylsilyl ether) and 7 and 8, (‘epimer 2’ and its trimethylsilyl ether), respectively.

Acid-catalyzed rearrangement of 7-hydroxyroyleanone into a 20(10→9) abeo-abietane derivative and two phenalenones Short treatment of either horminone (1b), taxoquinone (1a), 6,7-dehydroroyleanone (3) or 6β-hydroxyroyleanone (1c) with 80% H2SO4 at 0° leads to a mixture of rearranged products. Two of the structures, determined by X-ray-cristallography, were found to be (9R, 10R)-20(10→9)-abeo-12-hydroxy-5,7, 12-abietatriene-11,14-dione (4) and 9-isopropyl-2,2,5-trimethyl-8H-phenaleno[1,9-bc]furan-8-one (5), and the third compound, isolated in very small amounts, has been provisionally identified as 3-hydroxy-9-isopropyl-2,2,5-trimethyl-8H-phenaleno[1,9-bc]furan-8-one (6) from the spectroscopic data.

Syntheses of Optically Active Carotenoids with 3,5,6-Trihydroxy-5,6-dihydro β-End Groups For the specification of the relative and absolute configuration in carotenoids with 3,5,6-trihydroxy-5-6-dihydro β-end groups, several ionone derivatives and carotenoids bearing this end group were synthesized. Acid-catalyzed hydrolysis of (3S,5S,6R)– acetoxy-5,6-epoxy-5,6-dihydro-β-ionone (7) and of its (3S,5R,6S)-isomer (13) gave the diols 8 and 15, respectively, with exclusive inversion at c(5) (Scheme 2). Compared to this, mild acid hydrolysis of caroten-5-6-expoxides in the presence of H2O resulted in the formation of 5,6-diols with either inversion or retention of the configuration at C(6) (Scheme 3). Spectroscopic data allowed us to distinguish the relative configurations (3R*,5S*,6S*) (see A), (3R*,5R*,6R*) (see B), (3R*,5S*,6R*) (see C), and (3R*,5R*,6S*) (see D), of the 3,5,6-trihydroxy-5-6-dihydro β-end groups. Syntheses of the optically active carotene-hexols 20 and 21 and comparison with published data led to a revision of the structure of mectrazanthin (now formulated as 20), heteroxanthin (now formulated as 28), and further carotenoids with 3,5,6-trihydroxy end groups.

By using complementary and selectively acting reagents (TiCl4 and sulfurane 16), azafrin, the main carotenoid in the rhizomes of Escobedia scabrifolia, has been shown to have the (5R:6R)-configuration. Reaction of azafrinaldehyde (4) with (Ph3P)3RhCl leads to a mixture of 5 and 6, the latter arising probably through elimination of acetylene and recarbonylation.

Optically Active 4,5-Epoxy-4,5-dihydro-α-ionones; Synthesis of the Stereoisomeric 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-ϵ,ϵ-carotenes and the Steric Course of their Hydrolysis We prove that epoxidation with peracid of α-ionone, contrary to a recently published statement, predominantly leads to the cis-epoxide. Acid hydrolysis affords a single 4,5-glycol whose structure, established by an X-ray analysis, shows that oxirane opening occurred with inversion at the least substituted position (C(4)). Stable cis-and trans-epoxides are prepared by epoxidation of the C15-phosphonates derived from α-ionone. Both the racemic and optically active form are used for the synthesis of the 4,5:4′,5′-diepoxy-4,5,4′,5′-tetrahydro-ϵ,ϵ-carotenes having the following configuration in the end groups: meso-cis/cis, meso-trans/trans, rac-cis/trans, rac- and (6R, 6′ R)-cis/cis, rac- and (6R, 6′R)-trans/trans, rac- and (6R, 6′R)-cis/trans, and (6R, 6′ R)-cis/ϵ. Acid hydrolysis of the cis/cis-epoxycarotenoids under relatively strong conditions occurs again with inversion at C(4)/C(4′) in case of the cis/cis-epoxycarotenoids, but at C(5)/C(5′) in case of the trans/trans-epoxycarotenoids. An independent synthesis of this 4,5,4′,5′-tetrahydro-ϵ,ϵ-carotene-4,5,4′,5′-tetrol is presented. The irregular results of the oxirane hydrolysis are explained by assumption of neighbouring effects of the lateral chain. 400-Mz-1H-NMR data are given for each of the stereoisomeric sets. In the visible range of the CD spectra, the (6R, 6R′)-epoxycarotenoids compared with (6R, 6R′)-ϵ,ϵ-carotene exhibit an inversion of the Cotton effects.

Activated quinones: O- versus C-addition of phenols. New regiospecific syntheses of xanthones, thioxanthones and N-methyl-9-acridones The acid catalyzed reaction of phenols with activated quinones, e.g. 2-methoxycarbonyl-1, 4-benzoquinone or 2-acetyl-1, 4-benzoquinone, leads to substituted biphenylderivatives (C, C-addition) as has been previously described [1]. O, C-Addition of phenols has now been achieved by using 2-methoxypyridin or 4-dimethyl-aminopyridin [4] as basic catalysts. The resulting substituted diphenylethers can serve as convenient starting materials for regiospecific syntheses of substituted xanthones, especially for 1, 4-dimethoxyxanthones. Arylthiols and N-methyl-N-arylamines also react readily with activated quinones to give substituted di-aryl-thioethers and N-methyl-N, N-diarylamines respectively; both types of compounds are convenient materials for regiospecific syntheses of substituted thioxanthones and N-methyl-9-acridones.

Plectranthons A, B, C, and D. Diterpenoid Phenanthrene-1,4-diones from Leaf-glands a Plectranthus sp. (Labiatae) The following structures of four new 1,4-phenanthraquionones, isolated in minute amounts from the coloured leaf-glands of a Plectranthus sp. obtained from the borders of Lake Kiwu2, Rwanda, are proposed: plectranthon A (1; 3-hydroxy-5, 7,8-trimethyl-2-(2-propenyl)phenanthrene-1, 4-dione), plectranthon B (2; 2-(2ξ-acetoxypropyl)-3-hydroxy-5,7,8-trimethylphenanthrene-1,4-dione), plextranthon C (3; 3-hydroxy- 7,8-diemethyl-2-(2-propenyl)phenanthrene-1,4-dione), and plectranthon D (4; 3-hydroxy-7,8,10-trimethyl-2-(2-propenyl)phenanthrene-1,4-dione). 2-(2ξ-Hydroxypropyl)-3,6-dihydroxy-5,7,8-trimethylphenanthrene-1,4-dione (11), a compound very similar to 1–4, was prepared by a Wagner-Meerwein, rearrangement of coleon E (5). Biogenetically, the plectranthons are derived from abietanoic precursors. The compounds 1, 2 and 4 are the first natural C20-phenanthrenes of diterpenoid origin.

Syntheses of Carotenes with ψ-End Groups and (Z)-Configuration at Terminal Conjugated Double Bonds Five carotenes bearing (5Z)-ψ-end groups were synthesized and carefully characterized: (5Z)-lycopene (6), (5Z5′Z)-lycopene (7), (5′Z)-neurosporene (8), (5′Z)-β,ψ-carotene (12), and (5′Z)-e,ψ-carotene (14).

Syntheses of Aminolumazines 6-aminolumazien 2 (1-(6-amino-2,4,7-trioxo-1,2,3,4,7,8-hexahydropteridin-8-yl)-1-deoxy-D-ribitol), a degradation product of russupteridine-yellow I (1) has been prepared from l-deoxy-l-(2,4,7-trioxo-1,2,3,4,7,8-hexahydeopteridin-8-yl)-D-ribitol (5) via the azo compound 6 and its reduction with Sn/HCOOH. Condensation of 5-amono-6-(D-ribitylamino)uracil (8) with parabanic acid (9) has led to ta synthesis of russupteridine-yellow IV (4); l-deoxy-l-(2,6,8-trioxo-2,4,5,6,7,8-hexahydro-lH-imidazolo[4,5-g]pteridin-4-yl-D-ribitol), albeit in low yield.

Reinvestigation of the Carotenoids from Rosa foetida, structures of 12 Novel Carotenoids; Stereoisomeric Luteoxanthins, Auroxanthins, Latoxanthins and Latochromes From petals of the yellow Rosa foetida HERRM., more than 35 individual carotenoids were isolated and identified. Thereof, 87% belong to the expoxycarotenes. Structures were assigned for the first time to 4 auroxanthins ((8R,8′S), 6; (8S,8′S), 7; (8R,8′R), 8; (9Z,8R,8′R), 12), to 4 luteoxanthins ((8′R), 4; (8′S), 5; (9Z,8′R), 9; (9Z,8′S) 10(e)) and to novel latoxanthins and latochromes, very polar carotenoids having (3S,5R,6R)-trihydroxy β-end groups (latoxanthins 13 and 16, latochromes 14 and 15).

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,e-Carotene-3,3′-diol) and 3′,O-Didehydrolutein ( =(3R,6′R)-3-Hydroxy-β,e-carotene-3′-one) 3′.O-Didehydrolutein ( =(3R, 6′R)-3-hydroxy-β,e-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,e-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.

Leaf-gland Pigments: Coleon L, a New Diosphenolic Compound from Coleus somaliensis, S. MOORE; Revision of the Structures of Coleon H, I, I′ and K From leaf-glands of C. somaliensis a new, highly oxidized diosphenolic hydroquinone belonging to the abietane series was isolated in minute quantities. The new compound, coleon L (4c; C24H30O10), is very labile and transformed into its tautomer coleon K (5d) on standing in solution. 1H-NMR. spectra of coleon L showed clearly that the points of attachment of the two acetoxy groups are at C(3) and C(16) contrary to the positions expected from our previously published structure 3 for coleon K. Application of a recently elaborated conversion of trans-A/B-6,7-diketones of type 5 into the cis-isomers 6 allowed to assign unambiguously the β-configuration to the hydroxyl group at C(3) using pyridin induced solvent shifts. This confirmed structure 4c and 5d for coleon L and K, respectively. Based on similar reasons, the configuration at C(3) of coleon H, I and I′ had to be revised, the structures of these coleons being 4b, 5b and 5c, respectively.

Carotenoids in petals of Rosa foetida The petals of Rosa foetida, HERRM., a species of prime importance in the history of breeding true yellow garden roses, have been analysed for carotenoids for the first time. The following components were identified: β-carotene (1, 4,5%), lutein (2, 8%), zeaxanthin (3, 17,4%), auroxanthin (4, 30,8%), luteoxanthin (5, 21,9%), violaxanthin (6, 9,2%) and neochrome (7, 4,1%). Not identified carotenoids (4,1%) contained probably mutatoxanthin, antheraxanthin and apocarotenals. Thus the brillant yellow colour of R. foetida flowers is due mainly to carotenoid epoxides.