Solvent Extraction Studies of Two Isomeric 5, 7, 7, 12, 12, 14-Hexamethy-1, 4, 8, 11-Tetraazacyclotetradecanes

The distribution ratios of two isomeric 5, 7, 7, 12, 12, 14-hexamethyl-1, 4, 8, 11-tetraazacyclotetradecane, tet c and tet d, in several solvent systems at 25.0°C as functions of hydrogen ion concentration were determined. The protonation constants and the distribution constants of these macrocyclic ligands and their protonated species were obtained from the variations of the distribution ratios in the range of 6<–log [H⁺]<14.     

Metal Complexes with Macrocyclic Ligands. Part XLIII. Tetraazamacrocyclic nickel(II) and copper(II) complexes with aliphatic methylthio- and methoxy-substituted pendant chains

The 14-membered tetraazamacrocyclic Ni²⁺ and Cu²⁺ complexes of 4 (1, 4, 8-trimethyl-11-[(2-methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), 5 . (1, 4-dimethyl-8, 11-bis[2-(methylthio)ethyl]-l, 4, 8, 11-tetraazacyclotetradecane), and 7 (1, 4, 8, ll-tetrakis[2-(methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), with pne, two, and four methylthio-substituted pendant chains, respectively, and the Ni²⁺ complex of 6 (1, 4-dimethyl-8, 11-bis (2-methoxyethyl)-1, 4, 8, 11-tetraazacyclotetradecane), with two methoxy-substituted pendant chains, were synthesized and their chemistry studied with regard to modelling F430. Solution spectra in H₂O, MeCN, and DMF indicate participation of the side chain in metal coordination when the donor group is a thioether, whereas no coordination with the metal ion is observed with the ether group. Similarly the X-ray structures of the thioether-containing compounds [Ni( 5 )](ClO₄)₂, [Cu( 5 )](ClO₄)₂, and [Cu( 7 )](ClO₄)₂ show a coordination number of 5, whereas that of [Ni( 6 )](ClO₄)₂ with ether pendant chains, shows a coordination number of 4. Cyclic voltammetry of these complexes in MeCN reveals that Ni²⁺ is reversibly reduced to Ni⁺ between ?0.64 and ?0.77 V vs. SCE, the potential being influenced by the nature and number of the pendant chains. At more negative potentials, the thioether is cleaved, whereby a thiol is formed; the thiol is then oxidized at ca. + 0.8 V vs. SCE, when a glassy carbon electrode is used, or at ca. 0 V vs. SCE at a dropping Hg electrode. No cleavage of the ether bond in [Ni( 6 )](ClO₄)₂ is observed under similar conditions.     

Metal complexes with macrocyclic ligands,XVII. Synthesis of two key intermediates for the preparation of mono-N-functionalized tetraazamacrocycles and their metal complexes

With a modification of the cyclization procedure of Richman & Atkins [8] the two macrocycles 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane ( 8 ) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane ( 15 ) were prepared. After selective cleavage of the benzyl and trityl group, respectively, one obtains the two key products 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane ( 9 ) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane ( 16 ) which have three N-atoms protected by tosyl groups and one accessible for further reactions. To test some of the possibilities we have alkylated 9 and 16 with iodoacetamide, 1-tosyl-aziridine and acrylonitrile. After detosylation with HBr in glacial acetic acid in the presence of phenol mono-N-functionalized tetraazamacrocycles were thus obtained. The advantage of this synthesis is that the cyclization which is the most difficult step of the whole procedure, has to be done only once, regardless of the nature of the pendant arm. In addition a large number of derivatives can be prepared by varying the alkylation component. With Ni²⁺, Cu²⁺ and Zn²⁺ metal complexes of these new ligands were prepared and their IR. and VIS. spectra studied. In the case of the carbamoyl derivatives 12, 14 and 18 the Cu²⁺-complexes exist in two forms. Whereas at low pH the carboxamide group of the pendant arm is probably not bound to the metal ion, at high pH after deprotonation it coordinates in one of the axial positions.     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-acetyltropolones. Formation of heterocycle-fused troponoid compounds

3-Acetyltropolone ( 1 ) reacted with bromine, iodine, and nitric acid to afford respectively 3-acetyl-5,7-di-bromotropolone ( 2 ), 3-acetyl-7-iodotropolone ( 3 ), and 3-acetyl-5-nitro- ( 4 ) and 3-acetyl-5,7-dinitrotropolone ( 5 ). Azo-coupling reactions of 1 gave 3-acetyl-5-arylazotropolones 7a-f. The Schmidt reactions of 2 and 3 gave respectively 5,7-dibromo- ( 9 ) and 7-iodo-2-methyl-8H-cyclohept[d]oxazol-8-one ( 10 ), while 4 gave 3-acetamido-5-nitrotropolone ( 11 ). Compounds 2 and 4 reacted with hydroxylamine to give 3-methyl-8H-cyclohept[d]isoxazol-8-ones 12 and 13. The reactions of 2 , 3 , and 4 with hydrazine gave 3-methyl-1,8-dihydrocycloheptapyrazol-8-ones 15 , 16 , and 17.     

Valenzisomerisierung von cis-Dienonen,II. 5-Phenylpenta-2, 4-dienaldehyde [1]

The 5-Phenylpenta-2,4-dienaldehydes 4 , and 7 , show an uncatalized cis-trans-isomerization of the 4,5-double bond above 70 °C. The negative value of the activation entropy for these reactions points to the formation of the bicyclic valence isomeric 2H-Pyrans 5 and 8 respectively in the rate determining step. Intermediate 5 can be trapped as its tetracyanoethylene cycloadduct 11 . The cis-trans isomeric 1,6-diphenyl-hexa-1,3,5-trienes 12a and 12b undergo above 150° a disrotatory ring closure to the bicyclic dienes 13 and 14 respectively.     

Synthesis, crystal structure, and thermochemical behavior of the guest-host complex [(LH2)(BF4)2 H2O] (L = racemate-5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane)

The interaction between BF₃ (C₂H₅)₂Oand a racemate of 5,7,7,12,12,14-hexamethyl-l,4,8,11-tetraazacyclotetradecane (L) in the presence of air moisture leads to the complex [(LH ₂) BF₄)₂ - H₂O] (I), whose structure was determined by X-ray structure analysis and confirmed by thermogravimetric data. The crystals are monoclinic, C₁₆H₄₀B₂F₈N₄O, space group P2₁ln, a-25.570(7), b = 11.231(5), c = 8.715(4) å, α = 97.32(3)?, Z = 4, the final R value is 0.0753 for 2800 unique reflections. The structure is built from the double-charged organic cations of the tetraazamacrocycle, tetrafluoroborate anions, and water molecules (1:2:1) linked by a system of hydrogen bonds of NH...F, NH...O, and OH...F type, in which all the four macrocycle nitrogens perform the function of proton donors. The macrocycle in the complex has approximately C₂ symmetry.     

Synthesis of New Pyrido[4″,3″:4″,5″]thieno[2″,3″:4,5]pyrimido[2,1-b][1,3,4]thiadiazine Derivatives

Ethyl 2-methyl-11-oxo-9, 10-dihydro-1 H , 11 H -pyrido[4",3":4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 7 has been synthesised by the reaction of ethyl 3-amino-4-oxo-2-thioxo-1,3,4,5,6,8-hexahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7(2 H )-carboxylate 2 with allylbromide followed by treatment with bromine and subsequent dehydrobromination of the brominated product 5 with ethanolic sodium hydroxide. Its isomeric ethyl 2-methyl-11-oxo-9,10-dihydro-3 H ,11 H -pyrido[4",3Prime;:4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 8 has been obtained by condensation of 2 with chloroacetone followed by cyclization of the intermediate 9 with p -toulenesulfonic acid. The thiadiazino derivatives 11 , 13 , 15 were prepared through the reaction of 2 with the appropriate f -halocarbonyl compounds followed by cyclization reactions of the intermediates 10 , 12 , 14 .     

Diterpenoide Drüsenfarbstoffe aus Labiaten: Coleone U,V, W und 14-O-Formyl-coleon-V sowie 2 Royleanone aus Plectranthus myrianthus BRIQ.; cis- und trans-A/B-6, 7-Dioxoroyleanon

Leaf-gland Pigments: Coleons U, V, W, 14- O -Formyl-coleon-V, and two Royleanones from Plectranthus myrianthus BRIQ. ; cis - and trans -A/B-6,7-Dioxoroyleanones From leaf-glands of the South-African P. myrianthus (Labiatae) the following diterpenoids have been isolated and their structures established: coleon U, C₂₀H₂₆O₅ (6, 11, 12, 14-tetrahydroxy-abieta-5, 8, 11, 13-tetraene-7-one, 2a ); coleon V, C₂₀H₂₆O₅ (11, 12, 14-trihydroxy-abieta-8, 11, 13-triene-6, 7-dione, 4a ); coleon W, C₂₂H₂₈O₈ (16(or 17)-acetoxy-6, 11, 12, 14, 17 (or 16)-pentahydroxy-abieta-5, 8, 11, 13-tetraene-7-one, 6 ); 14-O-formyl-coleon-V, C₂₁H₂₆O₆ (14-formyloxy-11, 12-dihydroxy-abieta-8, 11, 13-triene-6, 7-dione, 4b ); 7α-formyloxy-6β-hydroxyroyleanone, C₂₁H₂₈O₆ (7α-formyloxy-6β, 12-dihydroxy-abieta-8, 12-diene-11, 14-dione, 1a ); the already known 6β, 7α-dihydroxyroyleanone ( 1c ) and a dimeric abietane derivative whose structure is not yet elucidated. This is the first record of a co-occurrence of coleons and royleanones in the same plant. In the course of chemical investigations of 4a and 4b the highly oxidized trans- and cis-A/B-6,7-dioxoroyleanones ( 5a and 5b ) were obtained.     

Semi‐synthesis and NMR spectral assignments of flavonoid and chalcone derivatives

Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin ( 4 ) and 2′,6′‐dihydroxy‐4′‐methoxy‐3′,5′‐dimethyl chalcone ( 7 ), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4′‐triacetoxy jaceosidin ( 10 ), 5,7,4′‐tripivaloyloxy jaceosidin ( 11 ), 5,7,4′‐trimethoxy jaceosidin ( 12 ), 2′,6′‐diacetoxy‐4′‐methoxy‐3′,5′‐dimethyl chalcone ( 13 ), 2′‐hydroxy‐4′‐methoxy‐6′‐pivaloyloxy‐3′,5′‐dimethyl chalcone ( 14 ), and 2′‐hydroxy‐4′,6′‐dimethoxy‐3′,5′‐dimethyl chalcone ( 15 ) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14 . The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin ( 4 ) and the acetylated derivative, 5,7,4′‐triacetoxy jaceosidin ( 10 ), showed modest antibacterial activity (32–128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd.     

两种膦酸甲氨基大环化合物的合成与性质

在浓盐酸存在下,1,4,7,10-四氮杂环十二烷和1,4,8,11-四氮杂环十四烷分别与亚磷酸、甲醛发生Mannich型反应,得到相应的N,N’,N”,N-四膦酸甲基1,4,7．10-四氮杂环十二烷（DOTP）和N,N’,N”,N-四膦酸甲基1,4,8,11-四氮杂环十四烷（TETP）。产物纯度较高。在不同的pH条件下测定1HNMR,考察化学位移的变化。     

Synthesis of Nanocrystalline Materials Based on the Bi2O3-TiO2 System

Russian Journal of General Chemistry - Nanocrystalline bismuth titanates Bi2Ti4O11 (115±5 nm), Bi4Ti3O12 (60±5 nm), Bi2Ti2O7 (105±5 nm), Bi8TiO14 (82±5 nm), and Bi12TiO20...     

Epimeric Isopavine N-Oxides from Roemeria refracta

Roemeria refracta DC. (Papaveraceae) of Turkish origin yielded two novel epimeric N-oxides, (?)-(5R, 11S,14R)-reframidine N-oxide ( = (?)-(5R, 11S,14R)-11,12-dihydro-14-methyl-11,5-(iminomethano)-5H -cyclohepta[1, 2-f: 4, 5-f′]bis[1,3]benzodioxole 14-oxide; 1 ) and (?)-(5R, 11S, 14S)-reframidine N-oxide ( = (?)-(5R, 11S, 14S)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxole 14-oxide; 2 ). The isolated (?)-roelactamine ( = (?)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-one, 4 ) is the first natural isopavinoid incorporating a lactam group. The epimeric (?)-15-(2-oxopropyl)reframidines ( = (?)-1-[11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]propan-2-ones; 5/6 ) and the epimeric (?)-ethyl (reframidin-15-yl)acetates ( = (?)-ethyl [11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]acetates; 7/8 ) are probably artifacts. (±)-Coclaurine ( 9 ), (±)-N-methylcoclaurine ( 10 ), (?)-roemeridine ( 11 ), and N-feruloyltyramine ( 12 ) are also isolated from R. refracta together with the previously reported bases. Specific ¹³C-NMR assignments are reported for the first time for the isopavines.     

Hydrogen bonded networks based on Ni(II)-tetraazamacrocycle (tet-b) complexes: synthesis,isolation and structural characterization of α -[Ni(tet-b)(Cl)](ClO4) and α -[Ni(tet-b)(en)](ClO4)2

Five- and six-coordinate, α-[Ni(tet-b)(Cl)](ClO₄) (1) and α-[Ni(tet-b)(en)](ClO₄)₂ (2) (tet-b?= C-racemic-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) complexes have been synthesized and isolated from the reactions of α-[Ni(tet-b)](ClO₄)₂, which has trans-V (1R,4R,8R,11R,7S,14S or 1S,4S,8S,11S,7R,14R) conformation, with t-Bu₄NCl and ethylenediamine (en), respectively. The complexes have been characterized by X-ray crystallography. The crystal structure of 1 shows a distorted trigonal bipyramidal (TBP) coordination geometry composed of four nitrogen atoms from tet-b and a chloro group with an N₄Cl chromophore about the nickel(II) ion. The complex cations of 1 are assembled by the perchlorate ions via N–H?···?O hydrogen bonding to form 1-D zigzag chains along the [001] direction. The chains are linked through intermolecular hydrogen bonding where the coordinated chloro group of the complex cation forms two-center double hydrogen bonds with the adjacent N–H groups of the macrocyclic ligand along the [100] direction, resulting in a two-dimensional α-network. The crystal structure of 2 shows a distorted octahedral coordination environment consisting of four nitrogen atoms from tet-b and two from en with an N₆ chromophore about nickel(II) ion. The crystal packing analysis shows that the complex cations, α-[Ni(tet-b)(en)]²⁺ are interconnected by perchlorate ions through conventional two-center (N)H?···?O, and bifurcated (N)H?···?O?···?H(N) hydrogen bonding.     

Lamellarins as Inhibitors of P‐Glycoprotein‐Mediated Multidrug Resistance in a Human Colon Cancer Cell Line

Chemical analysis of a Didemnum sp. (CMB‐01656) collected during scientific Scuba operations off Wasp Island, New South Wales, yielded five new lamellarins A1 ( 1 ), A2 ( 2 ), A3 ( 3 ), A4 ( 4 ) and A5 ( 5 ) and eight known lamellarins C ( 6 ), E ( 7 ), K ( 8 ), M ( 9 ), S ( 10 ), T ( 11 ), X ( 12 ) and χ ( 13 ). Analysis of a second Didemnum sp. (CMB‐02127) collected during scientific trawling operations along the Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 ( 14 ) and two known lamellarins G ( 15 ) and Z ( 16 ). Structures were assigned to 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 on the basis of detailed spectroscopic analysis with comparison to literature data and authentic samples. Access to this unique library of natural lamellarins ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) provided a rare opportunity for structure–activity relationship (SAR) investigations, probing interactions between lamellarins and the ABC transporter efflux pump P‐glycoprotein (P‐gp) with a view to reversing multidrug resistance in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were expanded to include the permethylated lamellarin derivative ( 17 ) and a series of lamellarin‐inspired synthetic coumarins ( 19 , 20 , 21 , 22 , 23 , 24 ) and isoquinolines ( 25 , 26 ), successfully revealed 17 as a promising new non‐cytotoxic P‐gp inhibitor pharmacophore.     

Kinetics and mechanism of gas‐phase pyrolysis of N‐aryl‐3‐oxobutanamide ketoanilides,their 2‐arylhydrazono derivatives,and related compounds

Rates and products of reaction and Arrhenius activation parameters were determined for the gas‐phase thermolysis of 14 substrates of the title compounds using sealed pyrex reactor tubes and HPLC/UV‐VIS to monitor substrate pyrolysis. The 14 compounds under study are N‐phenyl‐3‐oxo‐ ( 1 ), N‐(p‐chlorophenyl)‐3‐oxo‐ ( 2 ), N‐(p‐methylphenyl)‐3‐oxo‐ ( 3 ), and N‐(p‐methoxyphenyl)‐3‐oxobutanamide ( 4 ), in addition to (i) four substrates ( 5–8 ) obtained by the replacement of the pairs of methylene hydrogens at the 2‐position of compounds ( 1–4 ), each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives ( 9–11 ) in which Cl, CH₃, or OCH₃ groups are substituted at the para position of the phenylhydrazono moiety of compound 5 ; (iii) 3‐oxobutanamide (acetoacetamide, 12 ), N‐phenyl‐3‐oxo‐3‐phenylpropanamide ( 13 ), and N,N′‐diphenylpropanediamide ( 14 ). The reactions were conducted over 374–546 K temperature range, and the values of the Arrhenius log A(s^?1) and E_a(kJ mol^?1) of these reactions were, respectively, 12.0 ± 2.0 and 119.2 ± 17.0 for the ketoanilides ( 1–4, 12–14 ), and 13.0 ± 0.7 and 157.5 ± 8.6 for the arylhyrazono compounds ( 5–11 ). Kinetically, the arylhydrazono derivatives were found to be ca. 1.4 × 10³ to 5.7 × 10³ times less reactive than the parent ketoanilides. A mechanism is proposed to account for reaction products and to rationalize molecular reactivities. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 82–91, 2007     

Sesquiterpenoids from the Fruits of Alpinia oxyphylla and Their Anti‐Acetylcholinesterase Activity

Fourteen sesquiterpenoids were isolated from the fruits of Alpinia oxyphylla Miq . Their structures were elucidated based on NMR analyses (¹H, ¹³C, DEPT, ¹H,¹H‐COSY, HMQC, HMBC, and NOESY) and identified as 12‐nornootkaton‐6‐en‐11‐one ( 3 ), (+)‐(3S,4aS,5R)‐2,3,4,4a,5,6‐hexahydro‐3‐isopropenyl‐4a,5‐dimethyl‐1,7‐naphthoquinone ( 5 ), nootkatene ( 6 ), 9β‐hydroxynootkatone ( 7 ), 2β‐hydroxy‐δ‐cadinol ( 8 ), 4‐isopropyl‐6‐methyl‐1‐tetralone ( 11 ), oxyphyllone E ( 12 ), oxyphyllone D ( 13 ), oxyphyllanene B ( 15 ), oxyphyllone A ( 16 ), oxyphyllol E ( 17 ), (9E)‐humulene‐2,3;6,7‐diepoxide ( 18 ), mustakone ( 20 ), and pubescone ( 21 ). Among them, 3 was a new norsesquiterpenoid, 8 was a new natural product, and 5, 6, 11, 20, 21 were isolated from A. oxyphylla for the first time. Twenty sesquiterpenoids, 1 – 5 and 7 – 21 , were investigated for their in vitro acetylcholinesterase (AChE) inhibitory activities, including previously isolated seven sesquiterpenoids from A. oxyphylla, (11S)‐12‐chloronootkaton‐11‐ol ( 1 ), (11R)‐12‐chloronootkaton‐11‐ol ( 2 ), nootkatone ( 4 ), oxyphyllenodiol A ( 9 ), oxyphyllenodiol B ( 10 ), 7‐epiteucrenone B ( 14 ), and alpinenone ( 19 ). TLC‐Bioautographic assay indicated that 1 – 4, 7, 14, 16, 18, 19 , and 21 displayed anti‐AChE activities at 10 nmol. Microplate assay confirmed that 19, 18, 16 , and 21 displayed moderate‐to‐weak anti‐AChE activities at the concentration of 100 μM , and 19 was the most potent inhibitor with an IC₅₀ value of 81.6±3.5 μM . The presence of anti‐AChE sesquiterpenoids in A. oxyphylla may partially support the traditional use of this fruit for the treatment of dementia.     

Novel C9 and C11 Hydrocarbons from the Brown Alga Cutleria multifida; Sigmatropic and Electrocyclic Reactions in Nature. Part VI

In addition to the known C₁₁H₁₆ hydrocarbons multifidene ( 4 ), aucantene ( 2 ), and ectocarpene ( 5 ), the marine brown alga Cutleria multifida produces trace amounts of the C₉H₁₂ hydrocarbon 7-melhylcycloocta-1,3,5-triene ( 8 ) and its valence tautomer 7-methylbicyclo[4.2.0]octa-2,4-diene, A second novel C₉H₁₂ hydrocarbon is 6-vinyicyclo-hepta-1,4-diene ( 9 ), a lower homologue of ectocarpene ( 5 ). Among the C₁₁H₁₆ hydrocarbons, 7-((1E/Z)-prop-l-enyl)cycloocta-1,4-diene ( 10 / 11 ) is found for the first time. The structure of all new products is confirmed by synthesis and spectroscopic data. The biosynthesis of the new hydrocarbons 8 – 11 is obviously linked to the pathways which lead to the major products giffordene ( 7 ), (6S)-ectocarpene ((6S)- 5 ), and (4R,5R)-aucantene ((4R,5R)- 2 ). Consecutive reactions of certain thermolabile primary products proceed via electrocyclic ring closure, 3,3-sigmatropic rearrangement, or a 1,7-sigmatropic H-shift.     

Synthese der Phoracantholide K,O und M

Synthesis of Phoracantholide K, O and M Two 14membered ring lactones 3 and 4 and a 12membered ring lactone 5 isolated from the metasternal secretion of the eucalypt longicorn Phoracantha synonyma have been synthesized as racemic mixtures by the following method. Reaction of the dilithium derivative of 5-hexynoic acid (6) with threo-8-bromo-2,4-isopropylidenedioxyoctane (7) , followed by removal of the protecting group and esterification with diazomethane gave methyl-threo-11, 13-dihydroxy-5-tetradecy-noate (8) (s. Scheme 2). Partial hydrogenation of the triple bond in 8 with Lindlar Pd-catalyst, followed by saponification lead to (threo, Z)-11, 13-dihydroxy-5-tetra-decenoic acid (10) . The dihydroxy acid 10 was converted into the S-(2-pyridyl) thioate and cyclized in diluted benzene solution under the influence of silver ions to yield the corresponding 12- and 14-membered lactones in approximately equal amounts. Isomerization of the mixture with p-toluenesulfonic acid in methylene chloride yielded the 14-membered lactone (cis-11, 13–5Z)-11-hydroxy-5-tetradecen-13-olide almost exclusively. It proved to be identical in its properties with natural phoracantholide K (3). With 5-hexynoic acid and 7-tetrahydropyranyloxy-octyl bromide or 5-tetrahydropyranyloxy-hexyl bromide as starting materials (±)-phoracantholide O (4) and M (5) have been synthesized in an analogous manner.     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-cinnamoyltropolones. Formation of styryl-substituted heterocycle-fused troponoid compounds

3-Cinnamoyltropolone ( 1 ) reacted with bromine to afford 7-bromo- ( 2 ), 5,7-dibromo-3-cinnamoyltropolone ( 3 ), and 6,8-dibromo-4,9-dihydrocyclohepta[b]pyrane-4,9-dione ( 4 ) according to amount of the reagent. Iodination and nitration of 1 gave respectively 7-iodo- ( 5 ) and 5-nitro-3-cinnamoyltropolone ( 6 ). Azo-coupling reactions gave 5-arylazo-3-cinnamoyltropolones 7a-f . Compounds 1, 2, 3 and 5 reacted with hydroxylamine to give 3-styryl-8H-cyclohept[d]isoxazol-8-ones 10-13 , while 6 and 7a gave 5-nitro-3-styryl-8H-cyclohept[d]-isoxazol-8-one oxime ( 14 ) and 2-cinnamoyl-7-methoxy-4-phenylazotropone ( 15 ), respectively. The reactions of 1,3 , and 5 with phenylhydrazine gave 3-styryl-1,8-dihydrocycloheptapyrazol-8-ones 16-19 .     

Synthesis of (±)-4-Demethoxydaunomycinone by Double Diels-Alder Additions to 2, 3, 5, 6-Tetramethylidene-7-oxanorbornane

Sequential Diels-Alder additions of methylvinyl ketone and dehydrobenzene to 2, 3, 5, 6-tetramethylidene-7-oxanorbornane (4) yielded the (5, 12-epoxy-1, 2, 3, 4, 5, 6, 11, 12-octahydro-2-naphtacenyl) methyl ketone (10) which, in few steps was oxidized to a precursos of (±)-4-demethoxydaunomycinone. The preparations of two precursors of anthracyclinones, the (5-acetoxy-) and (12-acetoxy-1, 2, 3, 4-tetrahydro-2-naphtacenyl) methyl ketones (14, 15) are presented. The synthesis of 6, 13-epoxy-6, 13-dihydropentacene (8) is also reported.