Studies toward the total synthesis of the cytotoxic sponge alkaloid pyrinodemin A

[structure: see text]. The syntheses of the proposed structure of pyrinodemin A (1) and its cis double bond positional isomer (C15'-C16') in racemic form are described. The key reaction involved an intramolecular nitrone/double bond cycloaddition. Our results suggest that neither 1 nor its double positional isomer is the correct structure of pyrinodemin A     

Mirabiquinone,a new unsymmetrical binaphthoquinone from the sea urchin Scaphechinus mirabilis

Mirabiquinone [7,5′-anhydroethylidene-6,6′-bis(2,3,7-trihydroxynaphthazarin)], a new unsymmetrical binaphthoquinone, was isolated from the sea urchin Scaphechinus mirabilis along with the known symmetrical binaphthoquinones ethylidene-6,6′-bis(2,3,7-trihydroxynaphthazarin) and 7,7′-anhydroethylidene-6,6′-bis(2,3,7-trihydroxynaphthazarin). The structure of mirabiquinone was established using ¹H NMR, ¹³C NMR, HSQC and HMBC data, along with a spectroscopic analysis of its pentamethoxy derivative. Mirabiquinone and the symmetrical binaphthoquinones demonstrated excellent scavenging of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical.     

Asymmetric synthesis of double bond isomers of the structure proposed for pyrinodemin A and indication of its structural revision

Asymmetric synthesis of double bond isomers (+)-2 (delta(15',16')) and (+)-3 (delta(14',15')) of the structure (1) (delta(16',17')) proposed for pyrinodemin A, a cytotoxic bis-pyridine alkaloid with a unique cis-cyclopent[c]isoxazolidine moiety from a marine sponge, has been accomplished. Pyrinodemin A was indicated to be a 1:1 racemic mixture of 2 from comparison of C(18 )and chiral HPLC analysis for pyrinodemin A and the synthetic compounds as well as ESIMS data of oxidative degradation products of pyrinodemin A.     

Synthesis and characterisation of two new binaphthyl trisilanes

The synthesis and characterisation of two binaphthyl trisilanes is described. Reaction between 2,2′-dilithio-1,1′-binaphthyl and 1,3-dichlorohexamethyltrisilane gave 3,3,4,4,5,5-hexamethyl-4,5-dihydro-3H-3,4,5-trisilacyclohepta[2,1-a;4,3-a′]binaphthalene (3). Compound 3 was characterised by ¹H, ¹³C and ²⁹Si NMR spectroscopy and a crystal structure analysis. Reaction between 2,2′-dilithio-1,1′-binaphthyl and 1,3-bis(trifluoromethanesulfonyloxy)-1,1,2,3,3-pentamethyltrisilane, generated in situ by treatment of 1,3-diphenyl-1,1,2,3,3-pentamethyltrisilane with trifluormethanesulfonic acid, gave 3,3,4,5,5-pentamethyl-4,5-dihydro-3H-3,4,5-trisilacyclohepta[2,1-a;4,3-a′]binaphthalene (7). Analysis by ¹H, ¹³C and ²⁹Si NMR spectroscopy revealed that 7 had a very similar structure to 3.     

A novel solid support for the synthesis of 3-aminoalkylated oligonucleotides

A novel improved controlled pore glass (CPG) support based on the 2-(hydroxymethyl)-6-nitrobenzoyl (HMNB) protecting group was developed for the synthesis of 3^′-aminoalkylated oligonucleotides. The release of oligonucleotides with free 3^′-amino groups from the support is complete within 2 h at 55 °C in concentrated ammonia.     

1,1′,1′′-(2,4,6-Trihydroxybenzene-1,3,5-triyl)triethanone tautomerism revisited

It has recently been suggested that 1,1′,1′′-(2,4,6-trihydroxybenzene-1,3,5-triyl)triethanone may be tautomeric. Using ¹³C NMR chemical shifts and deuterium isotope effects on ¹³C chemical shifts, it is demonstrated that this is not the case. This compound occurs as a strongly hydrogen bonded benzene structure with hydrogen bonds between OH groups and the acetyl groups in both non-polar and hydrogen donating solvents. Quantum-chemical calculations using MP2 and M06-2X methods show substantial preference for the phenol structure in both the gas phase, and in cyclohexane and methanol. In addition, conventional UV–vis spectroscopy data suggest not tautomeric, but aggregation behaviour of the molecule in methanol and acetonitrile.     

Symbiodinolide, a novel polyol macrolide that activates N-type Ca channel, from the symbiotic marine dinoflagellate Symbiodinium sp.

A 62-membered novel polyol macrolide with a molecular weight of 2859 mu, symbiodinolide, was isolated from the symbiotic dinoflagellate Symbiodinium sp. Symbiodinolide exhibited a potent voltage-dependent N-type Ca²⁺ channel-opening activity at 7 nM and immediately ruptured the tissue surface of the acoel flatworm Amphiscolops sp. at 2.5 μM. The planar structure of symbiodinolide was elucidated by spectroscopic analysis and chemical degradations including hydrolysis and ethenolysis using the second-generation Grubbs' catalyst. Symbiodinolide was found to be a structural congener of zooxanthellatoxins. The relative stereochemistries of C26-C32, C44-C51, and C64-C66 parts, and the absolute stereochemistries of C69-73, C83-C103, and C3′-C18′ parts in symbiodinolide were established.     

Synthesis and structural investigation of 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline), 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) and a copolymer with methyl methacrylate by 1D and 2D NMR spectroscopy

Photo-responsive spiropyran-based compounds, such as, 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline) [OHSP], its monomer, such as 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) [MOSP] and its copolymers with methyl methacrylate [MMA] were synthesised using conventional synthetic routes. The copolymerisation was carried out either in tetrahydrofuran [THF] or in toluene using 2,2′-azobisisobutyronitrile [AIBN] as an initiator. The structures of these materials were investigated using ¹H and ¹³C NMR spectroscopy. DEPT-135, HCCOSW and COSY45 NMR experiments were used to assign and interpret the complex structure of spiropyran based materials.     

Synthesis and X-ray crystal structure analysis of the first nickel bisoxazoline pincer complex

The reaction in toluene between 2-iodo-1,3-bis(4′,4′-dimethyl-2′-oxazolinyl)benzene and Ni(COD)₂ gave [2,6-bis(4′,4′-dimethyl-2′-oxazolinyl)phenyl-N,C¹,N′]iodonickle(II) isolated in 69% yield. The structure of this novel nickel bisoxazoline pincer complex was confirmed by a X-ray crystal structure analysis.     

Photoreaction of iodouracil in DNA duplex; C-I bond is cleaved via two different pathways ‘homolysis and heterolysis’

We recently found that a selective photoreaction of 5-iodouracil (^IU) occurs in 5′-(G/C)AA^IU^IU-3′ and 5′-(G/C)A^IU^IU-3′ sequences in ^IU-substituted duplex DNA. In this study, the photoreactivity of the 5′-G(A)_n^IUT-3′ sequence was examined using various ^IU-containing oligonucleotides. HPLC analysis revealed that their photoreactivity largely depends on the number of As between G and ^IU. The most efficient reactivity was observed when the number of As was two and this decreased with increasing numbers from three to five, as observed for the 5′-G(A)_n^IUT-3′ sequence. These results indicate that the G located 5′ from ^IU acts as an electron donor for ^IU, as in the photoreaction of ^BrU. In sharp contrast to the ^BrU photoreaction, ^IU was photoreactive when the number of As was zero or more than five. These results indicate that both homolytic and heterolytic pathways operate in the formation of the uracil-5-yl radical in the photoreaction of ^IU in duplex DNA. In addition, the ratio of these pathways is highly dependent on DNA sequence.     

Thermal rearrangement of spiro[naphthalene(naphthopyranofurazan)]oxides to spiro[naphthalene(phenalenofurazan)oxides. A probable furazan oxide triggered tandem isomerisation process

Thermal rearrangement of (±)-spiro{naphthalene-1(2H),4′-(naphtho-[2′,1′:2,3]pyrano[4,5-c]furazan)}-2-one-11′-oxides in DMF or acetic anhydride at 140 °C gave an isomeric mixture of (±)-spiro{naphthalene-1(2H),1′-(5′-hydroxyphenalene[1,2-c]furazan)}-2-one-2′-oxides and 4′-oxides. The rearranged structure was confirmed from X-ray analysis and was consistent with the through space NOE data. The rearrangement is suggested to be an overall tandem isomerization process. Using variable temperature ¹H NMR spectroscopy the lower limit for the isomerisation barrier for a pair of tautomers was calculated to be 22 kcal mol⁻¹ at 423 K. The isomerisation equilibrium for a pair of isomers was studied by variable temperature ¹H NMR. The lower limit for the isomerisation barrier was calculated to be 22 kcal mol⁻¹ at 423 K. This low value may be indicative of the difficulty encountered in separating the isomers by chromatography. Semi-empirical AM1 and molecular mechanics calculations suggest that the (±)-spiro{naphthalene-1(2H),1′-(5′-hydroxyphenalene[1,2-c]furazan)}-2-one-2′-oxides are more stable than their 4′-oxide counterparts, in accordance to the X-ray structure. The lower population of the 4′-oxide isomers relative to that of the 2′-oxide isomers was explained in terms of an unfavourable intramolecular steric interaction found in the low energy structure of the former.     

Synthesis and conformation of a novel bridged nucleic acid having a trans-fused 3,5,8-trioxabicyclo[5.3.0]decane structure

A novel bridged nucleic acid analogue, 2′-deoxy-trans-3′,4′-BNA thymine monomer, was successfully synthesized. An ab initio calculation and X-ray structure analysis revealed that the trans-fused bicyclo[5.3.0]decane structure of the 2′-deoxy-trans-3′,4′-BNA effectively constrained the sugar puckering in C_2^′-endo with appropriate γ, δ and χ angles.     

Structure and absolute configuration of new acidic metabolites from Stachys ehrenbergii

Two novel metabolites have been isolated from the aerial parts of Stachys ehrenberiigii. Their structures and stereochemistry were elucidated using a combination of ¹³C and ¹H homo and heteronuclear 2D NMR experiments and mass analysis. The development of an enantioselective synthesis of 3-(2′-acetoxy-4-phenylbut-3′-enoylamino)propionic acid allowed to confirm the structure and assign the (R) absolute configuration at C-2′ of the natural product.     

Synthesis of regio- and stereoselective alkoxy-substituted spirobifluorene derivatives for blue light emitting materials

Three new octyloxy substituted spirobifluorenes, 2,7-diphenyl-3′,6′-bis(octyloxy)-9,9′-spirobifluorene (DPBSBF, 1a), 2,7-dibiphenyl-3′,6′-bis(octyloxy)-9,9′-spirobifluorene (DBBSBF, 1b) and 2,7-diterphenyl-3′,6′-bis(octyloxy)-9,9′-spirobifluorene (DTBSBF, 1c) were prepared. All the compounds had been fully characterized by ¹H and ¹³C NMR, UV-Vis, DSC, mass spectrometry and gave satisfactory elemental analyses. They possessed good solubility in common organic solvents and good homogeneous film formation. The optical energy band gap of DBBSBF was 3.27 eV between the HOMO energy level, 5.85 eV, measured by UPS and the LUMO, 2.58 eV, calculated from absorption spectrum. A blue organic light emitting diode (OLED) based on the structure of ITO/TPD (60 nm)/DBBSBF (40 nm)/Alq₃ (20 nm)/LiF (1 nm)/Al (100 nm) showed good performance. The luminance of 3125 cd/m² was observed at a drive voltage of 12.8 V and the colour coordinate in CIE chromaticity was (0.14, 0.12). The external quantum efficiency was obtained to be 2.8% at 100 cd/m².     

Synthesis of a new bidentate ferrocenyl N-heterocyclic carbene ligand precursor and the palladium (II) complex trans-[PdCl2(CfcC)], where (CfcC) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene

A new ferrocenyl-N-heterocyclic carbene ligand precursor 1,1′-bis[(1-tert-butylimidazolium)-3-methyl]ferrocene dichloride has been synthesised and structurally characterised. The imidazolium salt was readily deprotonated in situ with KN(SiMe₃)₂ and reacted with [PdCl₂ (cod)] to afford the structurally characterised palladium (II) complex trans-[PdCl₂(C^∧fc^∧C)], where (cod) = 1,5-cyclooctadiene and (C^∧fc^∧C) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene.     

Synthesis and electrochemical properties of bis(bipyridine)ruthenium(II) complexes bearing pyridinyl- and pyridinylidene ligands induced by cyclometalation of N′-methylated bipyridinium analogs

Ruthenium complexes with bipyridine-analogous quaternized (N,C) bidentate ligands [RuL(bpy)₂](PF₆)₂ (bpy = 2,2′-bipyridine, (1), L = L¹ = N′-methyl-2,4′-bipyridinium; (2), L = L² = N′-methyl-2,3′-bipyridinium) were synthesized and characterized. The structure of complex 2 was determined by the X-ray structure analysis. The ¹³C{¹H} NMR spectroscopic and cyclic voltammetric studies indicate that the coordination modes of these ligands are quite different, that is, the C-coordinated rings of (N,C)-ligands in 1 and 2 are linked to ruthenium(II) with a pyridinium manner and a pyridinylidene one, respectively. The ligand-localized redox potentials of 1 and 2 also revealed the substantial difference in the electron donating ability of both ligands.     

Synthesis and properties of oligomers containing substituted bithiazole rings

A series of novel polyimide and poly(Schiff base) oligomers containing substituted bithiazole rings were designed and synthesized, for the first time, by polycondensation of 5,5^′-dimethyl-2,2^′- diamino-4,4^′-bithiazole (MDABT) with dianhydrides (pyromellitic dianhydride, 3,3^′-4,4^′-benzophenone tetracarboxylic dianhydride and bis (3,4-dicarboxyphenyl) ether dianhydride), and dialdehydes (oxalic aldehyde, isophthalaldehyde and terephthalaldehyde). The structure of the oligomers was determined by IR and ¹H NMR spectroscopy, and elemental analysis. The oligomers showed good thermal stability. The Fe²⁺ complex of poly(Schiff base), synthesized from MDABT with oxalic aldehyde (PMTOA), was prepared with 13.7% Fe content and found to be a ferromagnet at low temperature.     

Stereochemistry of the insertion of disubstituted alkynes into the metal aminocarbyne bond in diiron complexes

Terminal alkynes (HCCR^′) (R^′=COOMe, CH₂OH) insert into the metal-carbyne bond of the diiron complexes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)(NCMe)(Cp)₂][SO₃CF₃] (R=Xyl, 1a; CH₂Ph, 1b; Me, 1c; Xyl=2,6-Me₂C₆H₃), affording the corresponding μ-vinyliminium complexes [Fe₂{μ-σ:η³-C(R^′)CHCN(Me)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R=Xyl, R^′=COOMe, 2; R=CH₂Ph, R^′=COOMe, 3; R=Me, R^′=COOMe, 4; R=Xyl, R^′=CH₂OH, 5; R=Me, R^′=CH₂OH, 6). The insertion is regiospecific and C-C bond formation selectively occurs between the carbyne carbon and the CH moiety of the alkyne. Disubstituted alkynes (R^′CCR^′) also insert into the metal-carbyne bond leading to the formation of [Fe₂{μ-σ:η³-C(R^′)C(R^′)CN(Me)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R^′=Me, R=Xyl, 8; R^′=Et, R=Xyl, 9; R^′=COOMe, R=Xyl, 10; R^′=COOMe, R=CH₂Ph, 11; R^′=COOMe, R=Me, 12). Complexes 2, 3, 5, 8, 9 and 11, in which the iminium nitrogen is unsymmetrically substituted, give rise to E and/or Z isomers. When iminium substituents are Me and Xyl, the NMR and structural investigations (X-ray structure analysis of 2 and 8) indicate that complexes obtained from terminal alkynes preferentially adopt the E configuration, whereas those derived from internal alkynes are exclusively Z. In complexes 8 and 9, trans and cis isomers have been observed, by NMR spectroscopy, and the structures of trans-8 and cis-8 have been determined by X-ray diffraction studies. Trans to cis isomerization occurs upon heating in THF at reflux temperature. In contrast to the case of HCCR^′, the insertion of 2-hexyne is not regiospecific: both [Fe₂{μ-σ:η³-C(CH₂CH₂CH₃)C(Me)CN(Me)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R=Xyl, 13; R=Me, 15) and [Fe₂{μ-σ:η³-C(Me)C(CH₂CH₂CH₃)CN(Me)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R=Xyl, 14, R=Me, 16) are obtained and these compounds are present in solution as a mixture of cis and trans isomers, with predominance of the former.     

Proton NMR study on two structures of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine in aqueous solution

The solution structure of one of dithymidine monophosphate (TpT) analogues, containing an (N-acetyl)imino backbone linkage (NCOCH₃) of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine (T_NT), has been determined by proton NMR. Two structures, designated as major and minor forms, in a ratio of about 3:2 coexist when the solution temperature is <25°C. Both forms adopt anti conformation with respect to the glycosidic bond, S-type deoxyribofuranose pucker, and have no base stacking. The backbone torsion angles ε′, φ_ON, φ_NC, and γ′ are trans, gauche⁺, gauche⁺, and gauche⁺ for the major form; and gauche⁻, gauche⁻, gauche⁻, and gauche⁺ for the minor form. Only major form is found at >25°C.     

Novel bifluorene based conjugated systems: synthesis and properties

A series of novel bifluorene based systems was synthesised by a convergent approach by means of a Suzuki cross-coupling between 7,7′-bis-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-9,9,9′,9′-tetraoctyl-2,2′-bifluorene and suitable aryl-bromides. All the oligomers have been characterized by ¹H, ¹³C NMR, FT-IR, UV-vis, PL spectroscopy and mass analyses. In particular, it has been demonstrated that the presence of strong electron donor (amines) or withdrawing (carboxylic esters) groups causes a bathochromic shift of the optical properties with respect to those of unsubstituted molecules. The effects of these functional groups on the HOMO-LUMO energy levels were investigated by cyclic voltammetry. Remarkably, the LUMO energy level of 7,7′-bis-[5′-carbodecaoxy-2,2′-bithiophen-5-yl]-9,9,9′,9′-tetraoctyl-2,2′-bifluorene (−3.07 eV) is strongly influenced by the presence of the ester functional group.