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).     

New heteroorganic betaines containing the (+)E15—C—E14—X(–) and (+)E15—C—E14(–) structural fragments (E15 = P,As; E14 = Si,Ge, Sn; X = C,S, O,NR)

The review surveys the data on the reactions of phosphorus and arsenic ylides with compounds containing E=X bonds (E = C, Si, Ge, or Sn; X = C or S), cyclic oligomers (R₂ES)_n (n = 2 or 3), and heavier analogs of carbenes. These reactions give rise to two new classes of heteroorganic betaines containing the ⁽⁺⁾E¹⁵—C—E¹⁴—X^(–) (I) and ⁽⁺⁾E¹⁵—C—E^14(–) (II) (E¹⁵ = P or As; E¹⁴ = Si, Ge, or Sn; X = C or S) structural fragments. Procedures for the synthesis of these compounds, their reactivities, the X-ray diffraction structures, and the electronic structures established by high-level quantum-chemical calculations are considered in detail. The carbon analogs of betaines of type I, viz., compounds bearing the ⁽⁺⁾P—C—C—X^(–) fragment (III), are also discussed. The latter were long considered as possible intermediates in the reactions of compounds containing the polar C=X bond (X = C, O, S, NR, etc.) with phosphorus ylides (classical Wittig and Corey—Chaykovsky reactions and related processes).     

Photochemical Reactions 151st Communication. Photo-oxygenation of (E)- and (Z)-7-Methyl-β-ionone

Photo-oxygenation of (E)-7-methyl-β-ionone ((E)? 1 ) and (E)-8-methyl-β-ionone ((E)? 2 ) gave rise to the formation of the hydroperoxy-enones (E)? 10 and (E)? 15 , respectively, which, in part, underwent intramolecular epoxidation to the hydroxy-epoxy-ketones 11 and 16 , respectively, The product distribution of the photo-oxidation of (Z)? 1 shows a marked influence of the skewed ground-state conformation of the dienone chromophore. Thus, singlet oxygen (¹O₂) was added to C(γ) of the dienone chromophore leading to the spirocyclic peroxy-hemiacetal 12 and to the endoperoxide 13 . In addition, the tricyclic peroxide 14 was formed as a new type of product via primary addition of ¹O₂ to C(γ) of the dienone chromophore. The structure of 14 was established by X-ray crystal-structure analysis of the hemiacetal 22 .     

Homo-atomic Nine-vertex Polyhedra of Group XIV Elements. Crystal structures and paramagnetic properties of [K-(2,2,2-crypt)]6E9E9 · 1.5 ethylenediamine · 0.5 toluene,E = Sn and Pb

The extractions of alloys of the nominal composition “KE_2.25” with ethylenediamine (en), (2,2,2)crypt, and toluene (tol) lead in good yields to paramagnetic compounds of the composition [K-(2,2,2-crypt)]₆E₉E₉ · 1.5 en · 0.5 tol (E = Sn ( 2 b ), Pb ( 2 c )). X-ray single crystal structure analyses show that two different E₉ clusters per asymmetric unit are present with configurations of distorted tricapped trigonal prismatic polyhedra. 2 b : space group P2₁/c (No. 14), Z = 4, a = 28.042(8), b = 23.527(5), c = 27.703(8) Å, β = 93.46(2)°; 2 c : space group P2₁/c (No. 14), Z = 4, a = 28.356(8), b = 23.757(5), c = 27.885(8) Å, β = 94.01(2)°.     

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.     

Octahedral Tin(IV) Complexes of the Chalcogen‐Centered Ligands [EC(PPh2S)2]2– (E = S,Se)

The metathetical reactions between SnBr₄ and Li₂[E'C(PPh₂E)₂] in toluene produce the homoleptic tin(IV) complexes Sn[E′C(PPh₂E)₂]₂ [E = E′ = S ( 1b ); E = S, E′ = Se ( 1c )], which were isolated as red crystals and structurally characterized by X‐ray crystallography. The metrical parameters of these octahedral complexes are compared with those of the all‐selenium analog Sn[E′C(PPh₂E)₂]₂ (E = E′ = Se, 1a ), which was prepared previously by a different route.     

Biosynthesis of cytochalasans. Part 4. The mode of incorporation of common naturally-occurring carboxylic acids into cytochalasin D1.

Utilization of sodium [1-¹⁴C]-, [2–¹⁴C]-, and [1,2-¹³C]-acetates, [1-¹⁴C]-, [1-¹³C]-, or [2-¹⁴C]-propionates, [1-¹⁴C]-or [2-¹⁴C]-malonates, of [1-¹⁴C]- or of [1-¹⁴C]-myristic acid, or of [1-¹⁴C]- and [1-¹⁴C]-palmitic acid in the biosynthesis of cytochalasin D ( 1 ) by Zygosporium masonii was determined by degradation studies or by carbon magnetic resonance spectroscopy. The precursors were incorporated primarily via the acetate-malonate pathway to generate 1 from nine intact acetate units, eight of which are coupled in a head to tail fashion to form the C₁₆-polyketide moiety.     

Experimente zum kompetitiven Einbau der Stereoisomeren des Farnesols in Cantharidin. 6. Mitteilung zur Biosynthese des Cantharidins

Experiments on the competitive incorporation of farnesol-stereoisomers into cantharidin Farnesol ( 2 ) has been demonstrated to be an efficient precursor for cantharidin ( 1 ), into which it is transformed by elimination of C(1), C(5), C(6), C(7) and C(7′) [1]. The following incorporation experiments with doubly labelled (³H and ¹⁴C) stereoisomers of farnesol present strong evidence that (E,E)- farnesol ((E,E)- 2 ) in fact is the precursor for cantharidin, whereas (2E, 6Z)- 2 and (Z,Z)- 2 are not utilized for the biosynthesis of cantharidin. A possible mechanism for the incorporation of (2Z,6E)-farnesol ((2Z,6E)- 2 ) to an extent of 56,8% relative to (E,E)- 2 is discussed.     

Heterometall-Komplexe mit E6-Liganden (E = P,As)

Heterometallic Complexes with E₆ Ligands (E = P, As) The reaction of [Cp*Co(μ-CO)]₂ 1 with the sandwich complexes [Cp*Fe(η⁵-E₅)] 2 a: E = P, 2 b: E = As in decalin at 190°C affords besides [CpCo₂E₄] 4: E = P, 7: E = As and [CpFe₂P₄] 5 the trinuclear complexes [(Cp*Fe)₂(Cp*Co)(μ-η²-P₂)(μ₃-η^1:2:1-P₂)₂] 3 as well as [(Cp*Fe)₂(Cp*Co)(μ₃-η^2:2:2-As₃)₂] 6 . With [Mo(CO)₅(thf)] 3 and 6 form in a build-up reaction the tetranuclear clusters [(Cp*Fe)₂(Cp*Co)E₆{Mo(CO)₃}] 10: E = P, 11: E = As. 3, 6 and 11 have been further characterized by an X-ray crystal structure determination.     

Über die Temperaturabhängigkeit der 13C-NMR.-Spektren von [5–6-η-(1Z, 5E)-Cyclooctadien]tetracarbonyleisen und (1Z, 5E)-Cyclooctadien

On the Temperature Dependence of the ¹³C-NMR. Spectra of [5-6-η-(1Z,5E)-Cyclooctadien] and of (lZ, 5E)-Cyclooctadiene The activation parameters of the conformational ring inversion process (simultaneous rotation around the C(3), C(4) and C(7), C(8) bonds; cf. Scheme 1) of the title compounds ( 1 and 2 , respectively) have been determined between 275 L and 155 K by a complete line shape analysis of the temperature dependent proton noise-modulated decoupled ¹³C-NMR. spectra of 1 and 2 . The temperature dependence of the rates (k( 1 ) and k( 2 ), respectively) of the inversion process can be described by the following equations (no influence of the solvents was observed; E_a in J/mol): . Further data are given in Tables 1 and 2. The carbonyl groups of the complex 1 show at 180 K , where the ring inversion process is frozen out, a single line at 211 ppm, i. e. the coalescence temperature of the carbonyl groups must be < 180 K .     

Un nouvel exemple de transposition: l'épimérisation en C(3) d'hydroxy-3-δ1-pyrazolines dérivées de sucres

A Novel Example of Reversible Ring Opening: The Epimerization at C(3) of Sugar 3-Hydroxy-Δ¹-pyrazolines Reaction of 1 (either geometrical isomer) with hydrazine followed by in situ Ag₂O oxidation led to two pairs of interconverting isomers 4 ? 5 and 6 ? 7 . By the same treatment, (Z)- 10 and (or) (E)- 10 gave the pair 11 ? 12 . Acetylation of 4 ? 5 led to a non interconverting mixture of 8 and 9 . This fact, and the lack of incorporation of ¹⁸O when the epimerization took place in the presence of H₂¹⁸O indicated that the most probable mechanism consisted in a reversible ring opening ( D ? E ? F ). The kinetic parameters of these reactions are given and structural assignments proposed for the new compounds.     

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%).     

The synthesis and characterization of ( E,E )-dioxime and its transition metal complexes containing 12-membered macrocycles linked to ferrocenyl-methyl groups

13,14-bis(Hydroxyimino)-4,7-bis(ferrocenylmethyl)-2,3,4,5,6,7,8,9-octahydrobenzo[k]-4, 7-diaza-1,10-dithiacyclododecine[13,14-g]-quinoxaline (H₂L) has been prepared from (E,E)-dichloroglyoxime and 12,13-diamino-4,7-bis(ferrocenylmethyl)-2,3,4,5,6,7,8,9-octahydrobenzo[k]-4,7-diaza-1,10-dithiacyclododecine which was synthesized from 12,13-dinitro-4,7-bis(ferrocenylmethyl)-2,3,4,5,6,7,8,9-octahydrobenzo[k]4,7-diaza-1,10-dithia cyclododecine. Mononuclear nickel(II) and copper(II) complexes of H₂L have a metal-ligand ratio of 1?:?2 and the ligand coordinates through two nitrogen atoms, as do most (E,E)-dioximes. The homotrinuclear [Cu(L)₂Cu₂(dipy)₂](NO₃)₂ compound coordinates to the other two copper(II) ions through deprotonated oximate oxygens and two 2,2′-dipyridyl as an end-cap ligand to yield the trinuclear structure. The ligand and its complexes have been characterized on the basis of ¹H, ¹³C NMR, IR and MS spectroscopy and elemental analyses.     

The synthesis and characterization of a new (<Emphasis Type="Italic">E,E</Emphasis>)-dioxime containing 13-membered dithiadiazamacrocyclic moieties and its mononuclear complexes

A new (E,E)-dioxime, (6Z,7Z)-15,16-dihydro-14H-dibenzo[b,h][1,10,4, 7]dithiadiazacyclotride-cine-6,7(5H,8H)-dionedioxime (H ₂ L) has been synthesized by reacting cyanogen-di-N-oxide (2) with 2,2′-[propane-1,3-diylbis(thio)]dianiline (1). Mononuclear complexes (4) and (5) of this ligand have been synthesized by reacting the vic-dioxime (H₂L) with NiCl₂ · 6H₂O and CoCl₂ · 6H₂O, respectively. The BF ₂ ⁺ capped Ni(II) and Co(III) complexes (6) and (7) of the dioxime have been synthesized from (4) and (5). The new compounds were characterized by a combination of elemental analysis, ¹H- and ¹³C-n.m.r, i.r. and m.s. spectral data.     

Zur Biosynthese der Rubratoxine

In order to check the hypothesis that rubratoxin B ( 2 ), a C₂₆-metabolite, is formed biogenetically by head-to-tail coupling of two identical C₁₃-precursors derived from decanoic acid and oxaloacetic acid, two labelled forms of the postulated C₁₃-intermediate 2-((E)-1'-octenyl)-3-[¹⁴C]methyl- and 2-((E)-1'-octenyl)-3-[¹³C]-methylmaleic anhydride ( 10 ), were synthesized. The labelled compounds 10 as well as a number of other ¹⁴C]- and [¹³C]-labelled potential precursors were administered to growing cultures of Penicillium rubrum STOLL . Significant incorporation rates of acetate (as intact units) and malonate were observed. Propionate was incorporated after decarboxylation. Succinate exhibited the highest rate of incorporation. The results are in agreement with the assumption that the C₁₀-chain is formed by the fatty acid pathway and the C₃-unit via the tricarboxylic acid cycle. After administration of 10 randomization of the label was observed. Thus the question whether compound 10 is a biogenetic intermediate remains unanswered.     

(E)-9-Isopropyl-6-methyl-5,9-decadien-2-one,a Terpenoid C14-Ketone with a Novel Skeleton

(E)-9-Isopropyl-6-methyl-5,9-decadien-2-one (1a) , a terpenoid C₁₄-ketone with a novel skeleton, was isolated from costus root oil (Saussurea lappa CLARKE ) and its structure established by a two-step synthesis from thuja ketone ( 2 ). The possible role of the new compound as an intermediate in the biosynthesis of the irones is discussed.     

Vibrational Spectra of Cluster Anions. 2. Vibrational Spectra of Compounds with the Cluster Anions [E4]4−: M4E4 (M = K,Rb, Cs; E = Ge,Sn) and β‐Na4Sn4

Vibrational spectra of the compounds M₄E₄ (M = K, Rb, Cs; E = Ge, Sn) and of β‐Na₄Sn₄ with the cluster anions [E₄]^4? were analysed based on the point group of isolated tetrahedranide units. The lower individual symmetry of the anions in the real structure being more patterned and complex primarily affects the spectra of the tetrahedro‐tetragermanides. ν₃(F₂) clearly splits both in Raman and IR and in the case of K₄Sn₄ only in IR. Rb₄Sn₄ and Cs₄Sn₄ exhibit very simple spectra with three bands in Raman and one band in IR. The breathing mode ν₁(A₁) for the quasi isolated [E₄]^4? cluster appears only in the Raman spectrum and is hardly influenced by the structural environment and by the nature of the alkali metal cations: ν₁(A₁) = 274 cm^?1 ([Ge₄]^4?) and 183‐187 cm^?1 ([Sn₄]^4?), respectively. The calculated valence force constants f_d(E–E) are: [Ge₄]^4? : f_d = 0.89 Ncm^?1 ( K ), 0.87 Ncm^?1 ( Rb ), 0.86 Ncm^?1 ( Cs ) and [Sn₄]^4? : 0.67 Ncm^?1 ( Na ), 0.66 Ncm^?1 ( K ), 0.67 Ncm^?1 ( Rb ), 0.68 Ncm^?1 ( Cs ). Both, the frequencies and the force constants fit well into the range previously reported.     

Structure and formation of gaseous [C4H6O]+˙ ions: 1—The enolic ions [CH2C(OH)?CHCH2]+˙ and [CH2CH?CHCH(OH)]+˙ and their relationship with their keto counterparts

The [C₄H₆O]^+˙ ion of structure [CH₂?CHCH?CHOH]^+˙ (a) is generated by loss of C₄H₈ from ionized 6,6-dimethyl-2-cyclohexen-1-ol. The heat of formation ΔH_f of [CH₂?CHCH?CHOH]^+˙ was estimated to be 736 kJ mol^?1. The isomeric ion [CH₂?C(OH)CH?CH₂]^+˙ (b) was shown to have ΔH_f, ? 761 kJ mol^?1, 54 kJ mol^?1 less than that of its keto analogue [CH₃COCH?CH₂]^+˙. Ion [CH₂?C(OH)CH?CH₂]^+˙ may be generated by loss of C₂H₄ from ionized hex-1-en-3-one or by loss of C₄H₈ from ionized 4,4-dimethyl-2-cyclohexen-1-ol. The [C₄H₆O]^+˙ ion generated by loss of C₂H₄ from ionized 2-cyclohexen-1-ol was shown to consist of a mixture of the above enol ions by comparing the metastable ion and collisional activation mass spectra of [CH₂?CHCH?CHOH]^+˙ and [CH₂?C(OH)CH?CH₂]^+˙ ions with that of the above daughter ion. It is further concluded that prior to their major fragmentations by loss of CH₃˙ and CO, [CH₂?CHCH?CHOH]⁺˙ and [CH₂?C(OH)CH?CH₂]^+˙ do not rearrange to their keto counterparts. The metastable ion and collisional activation characteristics of the isomeric allenic [C₄H₆O]^+˙ ion [CH₂?C?CHCH₂OH]^+˙ are also reported.     

Photochemische Reaktionen 111. Mitteilung [1] Zur Photochemie α, β-ungesättigter γ, δ-Epoxyester I: Singulett- versus Triplettreaktivität

On triplet excitation (E)- 2 isomerizes to (Z)- 2 and reacts by cleavage of the C(γ), O-bond to isomeric δ-ketoester compounds ( 3 and 4 ) and 2,5-dihydrofuran compounds ( 5 and 19 , s. Scheme 1). - On singulet excitation (E)- 2 gives mainly isomers formed by cleavage of the C(γ), C(δ)-bond ( 6–14 , s. Scheme 1). However, the products 3–5 of the triplet induced cleavage of the C(γ), O-bond are obtained in small amounts, too. The conversion of (E)- 2 to an intermediate ketonium-ylide b (s. Scheme 5) is proven by the isolation of its cyclization product 13 and of the acetals 16 and 17 , the products of solvent addition to b . - Excitation (λ = 254 nm) of the enol ether (E/Z)- 6 yields the isomeric α, β-unsaturated ε-ketoesters (E/Z)- 8 and 9 , which undergo photodeconjugation to give the isomeric γ, δ-unsaturated ε-ketoesters (E/Z)- 10 . - On treatment with BF₃O(C₂H₅)₂ (E)- 2 isomerizes by cleavage of the C(δ), O-bond to the γ-ketoester (E)- 20 (s. Scheme 2). Conversion of (Z)- 2 with FeCl₃ gives the isomeric furan compound 21 exclusively.     

Vibrational Spectra of the Cluster Anions [E4]4– in the metallic Sodium and Barium Compounds Na4E4 and Ba2E4 (E = Si,Ge)

The vibrational spectra of the cluster anions [E₄]^4– (E = Si, Ge) in the metallic compounds Ba₂E₄ and Na₄E₄ have been measured and assigned based on the T_d symmetry of the discrete tetrahedranide anion. Due to the lower site‐symmetries in the respective crystals all degenerate modes are split, but to different extends. The characteristic breathing frequency ν(E–E) of the [E₄]^4– cluster appears exclusively in the Raman spectrum and is almost unaffected by the nature of counterions: ν(E–E) = 486 cm^–1 (E = Si) and 276 and 278 (Ge), respectively. The calculated valence force constants f_d (Si–Si) = 1.17 Ncm^–1 ( Na ); 1.15 Ncm^–1 ( Ba ) and f_d (Ge–Ge) = 0.98 Ncm^–1 ( Na ); 0.94 Ncm^–1 ( Ba ) are in good agreement with those previously reported.