Identification of farnesol as an intermediate in the biosynthesis of cantharidin from mevalonolactone

Identification of farnesol as an intermediate in the biosynthesis of cantharidin from mevalonolactone Simultaneous injection of 2-[¹⁴C]-mevalonolactone (2-[¹⁴C]- 1 ) and (E,E)-11′,12-[³H]-farnesol (11′,12-[³H]- 2 ) into Lytta vesicatoria L . (Coleoptera, Meloidae) yields doubly labelled cantharidin ( 3 ). The remainder of the precursor farnesol, re-isolated from the insects after the incubation period, has incorporated ¹⁴C-radioactivity. The labelling pattern in this farnesol, as determined by two independent degradative reaction sequences, is in agreement with the isoprene rule. Since specific incorporation of farnesol ( 2 ) into cantharidin ( 3 ), and of mevalonolactone ( 1 ) into both, farnesol ( 2 ) and cantharidin ( 3 ) is observed, the sesquiterpene alcohol 2 acts as an intermediate in the biosynthesis of the C₁₀-compound 3 (Scheme 1).     

Einbauversuche mit (3H und 14C)-doppelmarkiertem Farnesol in Cantharidin. 5. Mitteilung zur Biosynthese des Cantharidins

Incorporation experiments with (³H and ¹⁴C) doubly labelled farnesols into cantharidin After injection of 11′, 12-[³H]-7-[¹⁴C]-farnesol or 11′, 12-[³H]-5,6-[¹⁴C]-farnesol, the ³H-label is located specifically in the C(9)-methyl-group of cantharidin, whereas the ¹⁴C-labelling pattern follows an incorporation via acetic acid (Scheme 4). C-Atoms 5, 6 and 7 from the middle part of the farnesol molecule are utilized for cantharidin biosynthesis to an extent that is about 2.1–11% of the incorporation rate of the methyl groups C(11′) and C(12), depending on the position of the ¹⁴C-label in farnesol. These results confirm our earlier hypothesis [1] that the C₁₀-molecule cantharidin is biosynthesized from the C₁₅-precursor farnesol which is cleaved between C(1)–C(2), C(4)–C(5), and C(7)–C(8). The synthesis of 7-[¹⁴C]-farnesol and of 5,6-[¹⁴C]-farnesol is described.     

On the incorporation of geraniol and farnesol into cantharidin (author's transl)

On the incorporation of geraniol and farnesol into cantharidin Earlier investigations [1] have shown that cantharidin (1) is biosynthesized by the male Lytta vesicatoria L. (Meloidae, Coleoptera) from the common terpenoid precursors mevalonate and farnesol (3) . To prove if geraniol (2) is incorporated via farnesol (3) into cantharidin (1) the following geraniols have been synthesized and injected into either larvae or male adult Lytta vesicatoria, partly in a mixture with synthetic 11′, 12-[³H]-farnesol as an internal standard: 2-[¹⁴C]-, 7-[¹⁴C]-, 7′, 8-[¹⁴C]-, 7′, 8-[³H]-geraniol. Unexpectedly, geraniol (2) was not specifically incorporated into cantharidin (1) perhaps due to its higher toxicity or its faster degradation relative to the other precursors before incorporation. The incorporation of U-[¹⁴C]-leucine, U-[¹⁴C]-isoleucine and 1-[¹⁴C]-glucose into cantharidin (1) via their metabolites is evident by degradation studies, whereas 1-[¹⁴C]- and 2-[¹⁴C]-glycine do not serve as precursors for cantharidin (1) .     

Reduktion von 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzol: Synthese von Cyclotrisazobenzol ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaen)

Reduction of 1,2-Bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene¹: Synthesis of Cyclotrisazobenzene ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaene) Na₂S reduction of 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene ( 2 ) yielded 3 deoxygenated products: the (known) red 2,2′-((E,E)-1,2-phenylenbisazo)dianiline ( 3 , 23%), the orange 2-[2-((E)-2-aminophenylazo)phenyl]-2H-benzotriazol ( 4 , 55%) and the colorless 2,2′-(1,2-phenylene)di-2H-benzotriazol ( 5 , 13%). The constitutions of 3 – 5 and of 6 , the N-acetyl derivative of 4 , were deduced from their ¹H-NMR spectra (chemical shifts, couplings, and symmetry properties), and the configurations of 3 , 4 , and 6 at their N,N-double bonds are assumed to be the same as in 2 . Oxidation of 3 with 2 mol-equiv. of Pb(OAc)₄ afforded 5 (47%) and a novel, highly symmetrical macrocycle, called cyclotrisazobenzene ( 7 , 24%). The constitution of 7 as a tribenzo-hexaaza[12]annulene and its (E)-configuration at the N,N-bonds was confirmed by X-ray analysis. The molecular symmetry expressed by the ¹H-, ¹³C- and ¹⁵N-NMR spectra of 7 reveals a rapid torsional motion around the six N,C bonds. This implies that the N,N-double bonds in the cyclic 12π-electron system (or 24π-electron system if the benzene rings are included) of 7 are highly localized.     

Photochemical Reactions 150th Communication. Wavelength Dependence of the Photochemistry of 7-Methyl-β-ionone

The wavelength dependence of the photolysis of 7-methyl-β-ionone ((E)- 1 ) was investigated. Irradiation of (E)- 1 with light of λ > 347 nm leads primarily to (E/Z)-isomerization followed by transformation to the tricyclic enol ether 3 as the only secondary photoproduct. On photolysis of (E)- 1 with light of shorter wavelength (λ > 280 nm or λ = 254 nm), however, a series of other products was formed (via a) photocyclization of the dienone chromophore (→ 5 ), (b) photo-enolization (→ 8 ), and (c) a 1,5-sigmatropic H-shift (→ (E/Z)- 7 ). For the structure elucidation of the new products, 7-[¹³C]methyl-β-ionone ((E)-[7-methyl-¹³C]- 1 ) was prepared and irradiated furnishing the corresponding ¹³C-labelled photoproducts.     

Photochemical reactions. 137th communication. Preparation and photolysis of (E/Z)-7-methyl-β-ionone

The title compounds (E/Z)- 7 were prepared in 66% overall yield by reaction of β-ionone ((E)-( 1 ) with lithium dimethylcuprate, trapping of the intermediate enolate with benzeneselenenyl bromide and oxidation with H₂O₂. Analogously, (E/Z)-7-methyl-α-inone ((E/Z)- 12 ) was obtained in 65% yield from α-ionone ((E)- 11 ). ¹n, π^*- Excitation (λ > 347 nm, pentane) of (E)-7 causes rapid (E/Z)-isomerization and subsequent reaction of (Z)- 7 to 15 (66%). The formation of 15 is explained by twisting of the dienone chromophore due to repulsive interaction of the 7-CH₃-group with the CH₃-groups of the cyclohexene ring. On the other hand, irradiation λ > 347 nm, Et₂O) of (E)- 7 in the presence of acid leads to (Z)- 7 (5%) and to the novel compound 16 (88%).     

Biosynthesis of δ-Jasmin Lactone ( = (Z)-Dec-7-eno-5-lactone) and (Z,Z)-Dodeca-6,9-dieno-4-lactone in the Yeast Sporobolomyces odorus

(all-Z)-(9,10,12,13,15,16-²H₆)Octadeca-9,12,15-trienoic acid ( = α-linolenic acid; D₆- 4 ) was synthesized to investigate the biochemical formation of linolenic-acid-derived aroma compounds in cultures of the yeast Sporobolomyces odorus, using an established gas chromatographic/mass spectrometric (GC/MS) method. Three compounds were identified as labeled: (Z)-dec-7-eno-5-lactone (δ-jasmin lactone), (Z,Z)-dodeca-6,9-dieno-4-lactone, and (2E,4Z)-hepta-2,4-dienoic acid. Both lactones were biosynthesized mostly under conservation of the initial configuration from their corresponding oxygenated linolenic-acid intermediates. The application of (13S,9Z,11E,15Z)-13-hydroxy(9,10,12,13,15, 16-²H₆)octadeca-9,11,15-trienoic acid (D₆- 7 ) as a OH-functionalized precursor of δ-jasmin lactone allowed to gain insight into the stereochemical course of the biosynthesis to both enantiomers of this lactone. In this experiment, 88.3% of the metabolized labeled precursor was transformed under retention of the original configuration of the (R)-enantiomer. This investigation is also a contribution to a better understanding of the C?C bond isomerization steps which took place during the β-oxidative degradation of the substrate.     

Thermische (E), (Z)-Isomerisierungen bei substituierten Propenylbenzolen

Thermal (E), (Z)-Isomerizations of Substituted Propenylbenzenes The thermal isomerizations of (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)phenol ((E)- and (Z)- 3 ), (E)- and (Z)-N-methyl-2-(1′-propenyl)anilin ((E)- and (Z)- 4 ), (E)- and (Z)-3,5-dimethyl-2-(1′-propenyl)anilin ((E)- and (Z)- 5 , (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z- 6 ), (E)- and (Z)-2-(1′-propenyl)mesitylene ((E)- and (Z)- 7 ), (E)- and (Z)-2-(1′-propenyl)toluene ((E)- and (Z)- 8 ), (E)- and (Z)-4-(1′-propenyl)toulene ((E)- and (Z)- 9 ) as well as of (E)- and (Z)-2-(2′-butenyl)-mesitylene ((E)- and (Z)- 10 ) in decane solution were studied (Scheme 2). Whereas the isomerization of the 2-propenylphenols (E)- and (Z)- 3 occurs already between 130 and 150° (cf. Table 1), the isomerization of the 2-propenylanilins 4 and 5 takes place only at temperatures between 220 and 250° (cf. Tables 2 and 3). The activation values and the experiments using N-deuterated 4 (cf. Scheme 4) show that 2-propenylphenols and -anilins isomerize via sigmatropic [1,5]-hydrogen-shifts. For the isomerization of the methyl-substituted propenylbenzenes temperatures > 360° are required (cf. Tables 4 and 5). The activation values of the isomerization of (E)- and (Z)- 6 and (E)- and (Z)- 9 are in accord with those of other (E), (Z)-isomerizations which occur via vibrationally excited singlet biradicals (cf. Table 7). Nevertheless, thermal isomerization of 2′-d-(Z)- 8 (cf. Scheme 6) demonstrates that during the reaction deuterium is partially transfered into the ortho-methyl group, i.e. 1,5-hydrogen-shifts must have participated in isomerization of (E)- and (Z)- 8 (cf. Scheme 8). Under the equilibrium conditions 2,4,6-trimethylindan ( 17 ) is formed slowly at 368° from (E)- and (Z)- 6 , very probably via a radical 1,4-hydrogen-shift (cf. Scheme 9). In a similar way 2-ethyl-4,6-dimethylindan ( 19 ; cf. Table 6) arises from (E)- and (Z)- 7 . Thermolysis of (E)- and (Z)- 10 in decane solution at 367° results in almost no (E),(Z)-isomerization. At prolonged heating 19 and 2,5,7-trimethyl-1,2,3,4-tetrahydronaphthalene ( 20 ) are formed; these two products arise very likely from an intermolecular radical process (cf. Scheme 10).     

Caulerpenyne-Amine Reacting System as a Model for in vivo Interactions of Ecotoxicologically Relevant Sesquiterpenoids of the mediterranean-adapted tropical green seaweed caulerpa taxifolia

Caulerpenyne ( 1 ), the most abundant of the ecotoxicologically relevant sesquiterpenoids of the Mediterranean-adapted tropical green seaweed Caulerpa taxifolia, was found to react with Et₃N or pyridine in MeOH by initial deprotection of C(1)HO to give oxytoxin 1 ( 2a ), previously isolated from the sacoglossan mollusc Oxynoe olivacea. With BuNH₂, without any precaution to exclude light, 1 gave the series of racemic 3 and 4 , and achiral (4E,6E)- 5 , (4E,6Z)- 5 , (4Z,6E)- 5 , and (4Z,6Z)- 5 pyrrole compounds, corresponding to formal C(4) substitution, 4,5-β-elimination, and (E/Z)-isomerization at the C(4)?C(5) and C(6)?C(7) bonds. Changing to CDCl₃ as solvent in the dark, 1 gave cleanly, via 2a as an intermediate, 3 and (4E,6E)- 5 . The latter proved to be prone to (E/Z)-photoisomerization. Under standard acetylation conditions, 3 gave (4E,6E)- 5 via acetamide 7 as an intermediate. Particular notice is warranted by selective deprotection of 1 at C(1), mimicking enzyme reactions, and unprecedented formation of pyrrole compounds from freely-rotating, protected 1,4-dialdehyde systems.     

Photochemische Reaktionen. 118. Mitteilung [1] Zur vinylogen β-Spaltung von Enonen. UV.-Bestrahlung von 4-(3',7',7'-Trimethyl-2'-oxabicyclo [3.2.0]hept-3'-en-1'-yl)but-3-en-2-on

Vinylogous β-Cleavage of Enones: UV.-irradiation of 4-(3′,7′,7′-trimethyl-2′-oxabicyclo[3.2.0]hept-3′-ene-1′-yl)but-3-ene-2-on On ¹π,π*-excitation (λ = 254 nm) in acetonitrile (E/Z)- 2 is converted into the isomers 4–9 and undergoes fragmentation yielding 10 ; in methanol (E/Z)- 2 gives 7–10 and is transformed into 11 by incorporation of the solvent. On ¹π,π*-excitation (λ λ?347 nm; benzene-d₆) (E)- 2 is isomerized into (Z)- 2 , which is converted into the isomers 3 and 4 by further irradiation. ¹π,π*-Excitation (λ = 254 nm; acetonitrile) of 4 gives 6 and (E)- 9 , whereas UV.-irradiation (λ = 254 nm; acetonitrile-d₃) of 5 yields (E)- 7 and 8 . On ¹π,π*-excitation (λ = 254 nm; acetonitrile) of (E/Z)- 12 the compounds (E)- 14 and (E)- 15 are obtained.     

Azimine IV. Kinetik und Mechanismus der thermischen Stereoisomerisierung von 2,3-Diaryl-1-phthalimido-aziminen

Azimines IV. Kinetics and Mechanism of the Thermal Stereoisomerization of 2,3-Diaryl-1-phthalimido-azimines¹) Mixtures of (1E, 2Z)- and (1Z, 2E)-2-phenyl-1-phthalimido-3-p-tolyl-azimine ( 3a and 3b , resp.) and (1E, 2Z)- and (1Z, 2E)-3-phenyl-1-phthalimido-2-p-tolylazimine ( 4a and 4b , resp.) were obtained by the addition of oxidatively generated phthalimido-nitrene (6) to (E)- and (Z)-4-methyl-azobenzene ( 7a and 7b , resp.). Whereas complete separation of the 4 isomers 3a, 3b, 4a and 4b was not possible, partial separation by chromatography and crystallization led to 5 differently composed mixtures of azimine isomers. The spectroscopic properties of these mixtures (UV., ¹H-NMR.) were used to determine the ratios of isomers in the mixtures, and served as a tool for the assignment of constitution and configuration to those isomers which were dominant in each of these mixtures, respectively. Investigation of the isomerization of the azimines 3a, 3b, 4a and 4b within the 5 mixtures at various concentrations by ¹H-NMR.-spectroscopy at room temperature revealed that only stereoisomers are interconverted ( 3a ? 3b; 4a ? 4b) and that the (1E, 2Z) ? (1Z, 2E) stereoisomerization is a unimolecular reaction. These observations exclude an isomerization mechanism via an intermediate 1-phthalimido-triaziridine (2) or via dimerization of 1-phthalimido-azimines (1) , respectively. The 3-p-tolyl substituted stereoisomers 3a and 3b isomerized slightly slower than the 3-phenyl substituted ones 4a and 4b , an effect which is consistent with the assumption that the rate determining step of the interconversion of (1E, 2Z)- and (1Z, 2E)-1-phthalimido-azimines (1a ? 1b) is the stereoisomerization of the stereogenic center at N(2), N(3), either by inversion of N(3) or by rotation around the N(2), N(3) bond. The total isomerization process is assumed to occur via the thermodynamically less stable (1Z, 2Z)- and (1E, 2E)-isomers 1c and 1d , respectively, as intermediates in undetectably low concentrations which stay in rapidly established equilibria with the observed, thermodynamically more stable (1E, 2Z)- and (1Z, 2E)-isomers 1a and 1b , respectively. At higher temperatures, the azimines 3 and 4 are transformed into N-phenyl-N,N′-phthaloyl-N′-p-tolyl-hydrazine (8) with loss of nitrogen.     

Photochemische Reaktionen. 121. Mitteilung. Zur Photochemie von ε,ζ-Methano-α,γ-dienonen und 7,8-Methano-1,3,5-trienen

Photochemistry of ε,ζ-Methano-α,γ-dienones and 7,8-Methano-1,3,5-trienes Irradiation of the δ-cyclopropyl-dienone (E)- 6 (λ ≥ 347 nm) gives (Z)- 6, 10 (1,5-sigmatropic H-shift), (E/Z)- 9 (electrocyclic process involving C(ε), C(ζ)-cleavage) and 11 (ring opening). The corresponding 6-cyclopropyl-triene (E)- 7 gives on singlet excitation (δ > 280 nm) 14 (1,5-sigmatropic H-shift) and, to a smaller extent, the bicyclo [3.2.0] heptenyl-dienes (E/Z)- 13 . However, on triplet excitation (λ ≥ 347 nm, benzophenone) (E)- 7 gives (E/Z)- 13 as the main products. On both ¹π,π*- and ³π,π*-excitation, (Z)- 7 and 15 are formed in small amounts.     

A New Monomer for π‐Conjugated Polymers — Synthesis and Characterization of Bis((Z)‐5‐phenyl‐2‐phenylmethylidene‐1, 3‐dithiole‐4‐yl)monosulfane

Bis((Z)‐5‐phenyl‐2‐phenylmethylidene‐1, 3‐dithiole‐4‐yl)monosulfane ( 6 ), a molecule consisting of two diphenyldithiafulvene units connected by a sulfur bridge, was synthesized by the selective lithiation of (Z)‐4‐phenyl‐2‐phenylmethylidene‐1, 3‐dithiole ( 7a ) at the endocyclic double bond and by subsequent reaction of the lithiated intermediate with bis(phenylsulfonyl)sulfane. Since this reaction sequence proceeded with retention of configuration, of three possible isomers (E, E, Z, E, and Z, Z) only the Z, Z form was obtained. On the basis of the X‐ray structure analysis and the NMR‐spectroscopic characterization of 6 supplemented by the NMR parameters of (E)‐ and (Z)‐4‐phenyl‐2‐phenylmethylidene‐1, 3‐dithiole, it was demonstrated that two characteristic ⁵J coupling constants of the proton at the exocyclic double bond indicate the configuration (Z or E) of disubstituted dithiafuvene derivatives.     

Isolation of Toxic and Potentially Toxic Sesqui- and Monoterpenes from the Tropical Green Seaweed Caulerpa taxifolia Which Has Invaded the Region of Cap Martin and Monaco

The green seaweed Caulerpa taxifolia (VAHL ) C. AGARDH (Caulerpales), which, after its recent accidental introduction, is growing in the region of Cap Martin much more vigorously than in the tropics, is shown to contain the known sesquiterpenic toxins caulerpenyne ( 1 ) – in larger amounts than in tropical Caulerpales – and oxytoxin 1 ( 2 ). Novel, potentially toxic products isolated in small amounts from this seaweed include the sesquiterpenes taxifolial A ( = (5E)-6,10-dimethyl-2-[(E)2-oxoethylidene]undeca-5,9-dien-7- yne-1,3-diyl diacetate; 3 ), taxifolial B (= (1E,6E,10E)-3-[( Z )-acetoxymethylidene]-7, 11-dimethyl-12-oxododeca-1,6,10-trien-8-yne-1,4-diyl diacetate; 4 ), 10,11-epoxycaulerpenyne ( = (1E,6E)-3-[(Z)-acetoxymethylidene]-10,11-epoxy-7, 11-dimethyldodeca-1,6-dien-8-yne-1,4-diyl diacetate; 1:1 diastereoisomer mixture; 5 ), and taxifolial C ( = (2Z,6E)-3-formyl-7,11-dimethyldodeca-2,6,10-trien-8-yne-1,1, 4-triyl triacetate; 6 ), besides, as the first example of a monoterpene from the Caulerpales, taxifolial D ( = (2Z)-3,7-dimethylocta-2, 6-dien-4-ynal; 7 ).     

The Photoisomerization Behavior of the (4-Hydroxycinnamoyl)-spermidines

The photoisomerization behavior of three mono[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 1, 2 , and 3 , and three bis[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 4, 5 , and 6 , are investigated. The synthetic product (E)- 1 could be almost quantitatively (> 96%) converted into its isomer (Z)- 1 under UV light irradiation. In the cases of (E)- 2 and (E)- 3 , a mixture of (E)/(Z) ca. 1:2 was obtained, when the same conditions were applied. The comparison of their UV spectra provides the possible explanation for these different behaviors. Furthermore, it was noticed that the (Z) → (E) isomerization of the C?C bond took place during the purification by reverse-phase high-performance liquid chromatography (RP-HPLC), and the (E)/(Z)-mixture is thus inseparable. The same feature could be observed during the isolation of the (Z,Z)-N,N′-bis[3-(4-hydroxyphenyl)prop-2-enoyl]-spermidines, (Z,Z)- 4 , (Z,Z)- 5 , and (Z,Z)- 6 . Nevertheless, the fractions of (Z,Z)- 5 and (Z,Z)- 6 were in almost pure state collected, and their ¹-NMR spectra are presented.     

Photochemical reactions. 134th Communication. Photochemistry of 5,6-epoxy-5,6-dihydro-3,4-methano-β-ionone: Influence of a cyclopropane ring on the reactivity of an ylide intermediate

On ¹n,π*-excitation(λ > 347 nm), the diastereomeric methanoepoxyenones (E)- 6 undergo isomerization via C,O-cleavage of the oxirane leading to diastereomeric photoproducts ((E)- 5 →(E/Z)- 13 and 14 ; (E)- 6 →(E/Z)- 16 and 17 ). On ¹π,π*-excitation (λ = 254 nm) of either (E)- 5 ) or (E- 6 the photoproducts 9, 10 and 11 are formed. By laser flash photolysis (λ = 265 nm) the ylide intermediate 3 was detected, with a lifetime of 10 μs in MeCN at ambient temperature. Stern-Volmer analysis of the ylide quenching by MeOH disclosed that compounds 9 and 10 , but not 11 , arise from the ylide intermediate e .     

Ajanolide A, a new germacranolide fromAjania fruticulosa

A new germacranolide, ajanolide A, was isolated from aerial parts ofAjania fruticulosa by means of extraction with CHCl₃ and adsorption chromatography. This compound was identified as (1(10)E,3S,4Z,6R,7S,11R)-3-acetoxygermacra-1(10),4-dien-12,6-olide ((1S,7S,10R,13R)-7-acetoxy-4,8,13-trimethyl-11-oxabicyclo[8.3.0]trideca-4(E),8(Z)-dien-12-one) by X-ray diffraction analysis. 2D¹H−¹H (COSY) and¹³C−¹H (COSY) NMR spectroscopy was used for assigning the¹H and¹³C NMR signals in the spectra of ajanolide A. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 167–170, January, 1998.     

Configuration,Conformation, and Reactivity of Highly Functionalized Eunicellane Diterpenes Isolated from the Gorgonians Eunicella cavolinii and Eunicella singularis from Marseille

Eunicellane diterpenes with a C(7)=C(16) (Δ^7,16; see 17 – 19 ), (Z)‐C(7)=C(8) ((7Z)Δ^7,8; see 20 – 23 ), and (Z)‐C(6)=C(7) ((6Z)Δ^6,7; see 10 ) bond, an uncommon feature in the case of extensive functionalization at the cyclohexane ring and the latter exhibiting uncommon configurations, were isolated from the gorgonian Eunicella cavolinii from Marseille (Figs. 5 and 2). The gorgonian Eunicella singularis (=Eunicella stricta) from the same area gave (7Z)Δ^7,8, Δ^7,16, and (6E)Δ^6,7 analogs 24 , 25 , and 13 , respectively (Fig. 5 and Scheme). The (6E)Δ^6,7 moiety of 13 – characterized by a slow 180° conformational flipping (Fig. 3) that results in broadening of NMR signals – makes the macrocycle highly strained. This may explain the spontaneous conversion of 13 to the 6‐methoxy‐7‐hydroxy derivative 14 in the presence of MeOH at −20° in the dark (Scheme). The isomeric, deacylated analogue 10 showed only little broadening of NMR signals and proved stable, in accordance with the less strained nature of this compound (Fig. 4).     

Isolation by HPLC. and Identification by NMR. Spectroscopy of 11 mono-, di- and tri-cis isomers of an aromatic analogue of retinoic acid,ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6, 8-tetraenoate

Photoisomerization of an aromatic analogue of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6, 8-tetraenoate 1 in dilute solutions of hexane, benzene, and ethanol yielded multi-component mixtures of cis isomers which were separated by HPLC. FT-¹H-NMR. at 270 MHz and, in some cases, homonuclear decoupling and Overhauser experiments as well as ¹³C-NMR. were applied to establish the structures of 4 mono-cis, 4 (of 6 possible) di-cis, and 3 (of 4 possible) tri-cis isomers. The structures of 3 isomeric esters, namely (2Z, 4E, 6E, 8E) 6 , (2Z, 4Z, 6E, 8E) 9 , and (2Z, 4Z, 6Z, 8E) 7 were independently confirmed by direct syntheses. The ¹H-NMR. data of all these compounds and the ¹³C-NMR. data of the all-trans and of 6 cis isomers available in sufficiently large quantities are discussed.     

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).