Organometallic analogues of tamoxifen: Effect of the amino side-chain replacement by a carbonyl ferrocenyl moiety in hydroxytamoxifen

Since the widely prescribed selective estrogen receptor modulator (SERM) tamoxifen encounters growing cases of resistance in long-term treatments, alternative drugs with different therapeutic scopes have to be developed. Many investigators have modified the triphenylethylene scaffold, but very few have changed its amino side chain, essential for the antiestrogenic activity. For the first time, a lipophilic and stable organometallic entity, -OCH₂CO-[(η⁵-C₅H₄)FeCp], has replaced this key functional side chain, while keeping a good affinity for the estrogen receptor and an antiproliferative activity on cancer cells (MCF-7 and PC-3). Its mechanism of action is likely to be different from the antihormonal pathway followed by hydroxytamoxifen, and from the cytotoxicity observed for the ferrocifens.     

Synthesis and biochemical evaluation of 3,7-disubstituted farnesyl diphosphate analogues

Farnesyl diphosphate (FPP) analogues have proven to be both potent inhibitors of protein-farnesyltransferase (FTase) and valuable probes for the investigation of the function of prenylated proteins. Previously, we have demonstrated that certain 3-substituted and 7-substituted FPP analogues can act as inhibitors of FTase, while others are effective alternative substrates. We have now utilized our vinyl triflate-mediated route to synthesize the first seven FPP variants bearing substituents in both the 3- and 7-positions of the isoprene unit. Despite their exceptional steric bulk with respect to FPP itself, six of the seven analogues bind to FTase. Two of the analogues are potent inhibitors of the enzyme, but a more striking finding is that three FPP variants (4a, 4b, and 4f) are efficient alternative substrates for FTase.     

Synthesis and biochemical characterisation of fluorinated analogues of pepstatin A and grassystatin A

Pepstatin A and grassystatin A are natural, statine-containing peptides that act as inhibitors of aspartic protease enzymes. In this work, stereoselective fluorination is investigated as a strategy for enhancing the pharmacodynamic and pharmacokinetic properties of these lead compounds. Fluorination is found to modestly affect the protease inhibitory potency, leading to the identification of two highly active new inhibitors of the cancer-associated protease, cathepsin D. However, no dramatic changes are observed in terms of target selectivity, lipophilicity, membrane permeability or metabolic stability.     

金属有机配位聚合物的合成

金属有机配位聚合物(金属聚合物)由于整合了金属和聚合物的诸多优点而在清洁能源、智能响应材料、高性能器件制备方面具有广泛的应用潜力。本文综述了近十年金属聚合物合成进展,主要从聚合物形成和金属中心引入的顺序,如先合成聚合物再引入金属中心、先合成含金属单体后引发聚合以及一步法合成金属聚合物等方面进行论述,重点介绍合成方法、金属聚合物链结构和性能之间的关系,分析了不同合成方法的优缺点,探讨了金属聚合物合成的研究趋势。     

Organometallic chemistry of chiral diphosphazane ligands: Synthesis and structural characterisation

The diphosphazane ligands of the type, (C₂₀H₁₂O₂)PN(R)P(E)Y₂ (R = CHMe₂ or (S)-*CHMePh; E = lone pair or S; Y₂ = O₂C₂₀H₁₂ or Y = OC₆H₅ or OC₆H₄Me-4 or OC₆H₄OMe-4 or OC₆H₄Bu^t-4 or C₆H₅) bearing axially chiral 1,1'-binaphthyl-2,2′-dioxy moiety have been synthesised. The structure and absolute configuration of a diastereomeric palladium complex, [PdCl₂{ηsu2}-((O₂C₂₀H₁₂)PN((S)-*CHMePh)PPh₂] has been determined by X-ray crystallography. The reactions of [CpRu(PPh₃)₂Cl] with various symmetrical and unsymmetrical diphosphazanes of the type, X₂PN(R)PYY′ (R = CHMe₂ or (S)-*CHMePh; X = C₆H₅ or X₂ = O₂C₂₀H₁₂; Y=Y′= C₆H₅ or Y = C₆H₅, Y′ = OC₆H₄Me-4 or OC₆H₃Me₂-3,5 or N₂C₃HMe₂-3,5) yield several diastereomeric neutral or cationic half-sandwich ruthenium complexes which contain a stereogenic metal center. In one case, the absolute configuration of a trichiral ruthenium complex, viz. [Cp*Ruη₂-Ph₂PN((S)-*CHMePh)*PPh (N₂C₃HMe₂-3,5)Cl] is established by X-ray diffraction. The reactions of Ru₃(CO)₁₂ with the diphosphazanes (C₂₀H₁₂O₂)PN(R)PY₂ (R = CHMe₂orMe; Y₂=O₂C₂₀H₁₂or Y= OC₆H₅ or OC₆H₄Me-4 or OC₆H₄OMe-4 or OC₆H₄Bu^t-4 or C₆H₅) yield the triruthenium clusters [Ru₃(CO)₁₀{η-(O₂C₂₀H₁₂)PN(R)PY₂}], in which the diphosphazane ligand bridges two metal centres. Palladium allyl chemistry of some of these chiral ligands has been investigated. The structures of isomeric η³-allyl palladium complexes, [Pd(η³-l,3-R′₂-C₃H₃){η²-(rac)-(0₂C₂₀H₁₂)PN(CHMe₂)PY₂}](PF₆) (R′ = Me or Ph; Y = C₆H₅ or OC₆H₅) have been elucidated by high field two-dimensional NMR spectroscopic and X-ray crystallographic studies.     

Organometallic Tetrazole Derivatives: Preparation and Application to Organic Synthesis

The data are integrated and systematized on preparation procedures and application to the organic synthesis of organometallic tetrazole derivatives, including 5-metallated tetrazoles and tetrazoles with a metal-carbon bond in a substituent, and also organotin tetrazoles.     

Synthesis of Organometallic Compounds in Flow

Microreactor technology has proved to be an important technique in organic synthesis, especially when organometallic compounds are used, because it allows running rapid reactions with reactive and instable intermediates. This review will highlight the preparation of main‐group organometallic compounds deriving from Lithium, Magnesium, Zinc and Aluminum and their applications in flow conditions.     

Organometallic Aspects of the Fischer-Tropsch Synthesis

The Fischer-Tropsch Synthesis counts among the industrial-scale processes having a versatile and broad product range, and has for decades offered the most attractive possibility for the use of coal as a source of heating oil and fuels. This conceivably simple reaction, the catalytic hydrogenation of carbon monoxide, generally leads to simple hydrocarbons as well (i.e. short chain olefins) that have been sought as chemical feedstocks since the oil crisis of the seventies, but fails to provide the large-scale, economic process required, due in large part to the minimal selectivity of traditional Fischer-Tropsch processes. In an effort to solve this problem current research in this sector is concerned not only with the optimization of old and the development of new catalytic systems, but also increasingly with the elucidation of numerous relevant reaction mechanisms. This article will discuss, from the viewpoint of an organometallic chemist, the significance of typical model reactions, both with regard to some fundamental aspects of synthesis gas chemistry, and in comparison with previous views concerning the mechanism of the Fischer-Tropsch Synthesis. The importance of various unique classes of complexes that have been studied in the context of Fischer-Tropsch chemistry is also evaluated with regard to their importance in the synthesis of hydrocarbons from carbon monoxide and hydrogen. It emerges that the primary steps of the reductive oligomerization of carbon monoxide are best described by the carbide/methylene mechanism, as originally proposed by Hans Fischer and Franz Tropsch.     

A Different Approach to Enantioselective Organic Synthesis: Absolute Asymmetric Synthesis of Organometallic Reagents

Voilà, optical activity : Both enantiomers of 1‐chloroindene have been synthesized in high selectivity from solely achiral starting materials, and without using optically active catalysts (see scheme). These symmetry‐breaking syntheses provide a proof‐of‐concept for a new approach to asymmetric synthesis. NCS=N‐chlorosuccinimide.

     

Nucleic acid analogues: Synthesis and biomimetic reactions

Several nucleic acid analogues as shown in Scheme 1 were synthesized by alternating copolymerization of nucleoside analogues with maleic anhydride or acrylic anhydride. These polymers showed similar physicochemical properties to those of the natural polymers, such as base-pairing and base-stacking. Polymer 3U, for example, formed 1:1 complex with poly(adenylic acid) by base-pairing. Polymer 4A showed 33% of hypochromicity compared with the UV-absorption of adenosine due to the base-stacking. Polymer 5 catalyzed the cleavage of DNA and the hydrolysis of phosphodiester with a rate acceleration of 10³ compared with the uncatalyzed reaction.     

Synthesis of dihydrolysergol analogues

As a part of a search for novel biological active ergoline derivatives, the indole ring present in the ergoline skeleton (indole[4,3‐f,g]quinoline) was converted into different heterocyclic ring systems such as quinazoline 2 , benzofurane 3 and benzoxazole 4 . Due to the paramount importance of chirality to attain biological activity, natural dihydrolysergic acid 1 was chosen as starting material and a synthetic pathway conservative in term of chirality was followed.     

Synthesis of cyclosporin analogues

Analogues of Cyclosporin modified at positions 1 and/or 2 have been synthesised; synthesis of linear peptides was investigated by fragment condensation and stepwise synthesis and a number of cyclisation methods were evaluated.Synthesis of [(Me)(Thr¹)]-, (Hyp¹)-, (Hyp¹, Nle²)-, [(Me)Ser¹]-, (Me)Ser¹, Nle²]-, [(Me)Ser¹, Nva]- [(Me)Thr¹, Nle²]-, [(Me)Thr¹, Nva]-, [(Me)Ser¹, Thr²]- and [Dab¹]- Cyclosporins and constituent fragments are described.     

Synthesis and Reactivity of Organometallic Intermediates Relevant to Cobalt-Catalyzed Hydroformylation

Intermediates relevant to cobalt-catalyzed alkene hydroformylation have been isolated and evaluated in fundamental organometallic transformations relevant to aldehyde formation. The 18-electron (R,R)-(^iPrDuPhos)Co(CO)₂H has been structurally characterized, and it promotes exclusive hydrogenation of styrene in the presence of 50 bar of H₂/CO gas (1:1) at 100 °C. Deuterium-labeling studies established reversible 2,1-insertion of styrene into the Co−D bond of (R,R)-(^iPrDuPhos)Co(CO)₂D. Whereas rapid β-hydrogen elimination from cobalt alkyls occurred under an N₂ atmosphere, alkylation of (R,R)-(^iPrDuPhos)Co(CO)₂Cl in the presence of CO enabled the interception of (R,R)-(^iPrDuPhos)Co(CO)₂C(O)CH₂CH₂Ph, which upon hydrogenolysis under 4 atm H₂ produced the corresponding aldehyde and cobalt hydride, demonstrating the feasibility of elementary steps in hydroformylation. Both the hydride and chloride derivatives, (X=H⁻, Cl⁻), underwent exchange with free ¹³CO. Under reduced pressure, (R,R)-(^iPrDuPhos)Co(CO)₂Cl underwent CO dissociation to form (R,R)-(^iPrDuPhos)Co(CO)Cl.     

Organometallic compounds : LXIX. Synthesis and properties of the first chiral triorganostannyl-manganese complex

Methyl-1-naphthylphenylstannyltetracarbonyl(diphenyl-N-methyl-N-(S)-1-phenylethylaminophosphine)manganese (I) has been prepared by two different routes from racemic methyl-1-naphthylphenyltin chloride. Fractional recrystallizations yielded two diastereomeric fractions with fx205-1 = +40.3° and —71.4°, respectively, which have identical NMR and IR spectra.     

Synthesis of psoralens and analogues.

This review presents briefly the various classical syntheses of psoralens and angelicins which generally start from preformed suitably substituted coumarin or benzofuran derivatives. However, the discovery of the photocyclo-C-4 addition of psoralens to pyrimidine bases prompted new developments in this area. In particular, improved synthesis of psoralens and substituted angelicins, and synthesis of new analogues such as furochromenes, pyridopsoralens, pyrano benzopyrandiones, dioxinocoumarins and aza-psoralens were described recently. This review focuses on the chemical syntheses of these various compounds.     

Fe1−yO Nanoparticles: Organometallic Synthesis and Magnetic Properties

Non‐stoichiometric wüstite particles (Fe_1?yO) are synthesized using the controlled room‐temperature hydrolysis of the organometallic precursor {Fe[N(SiMe₃)₂]₂}. Particles stabilized by hexadecylamine with a diameter of ～5 nm are obtained. For such small nanoparticles, a distorted crystallographic structure is evidenced by wide‐angle X‐ray scattering at room temperature and reported for the first time. The study of the magnetic properties indicates that these particles are composed of an antiferromagnetic core surrounded by a ferromagnetic shell. According to the Néel theory, we demonstrate that this shell consists of 1.5 % of Fe³⁺ ions ferromagnetically coupled with Fe²⁺ ions.     

胞壁酰二肽(MDP)及其类似物的合成

本文报道胞壁酰二肽(MDP)及其类似物MDP[γ-Abu]^1、MDP-Oxalys的合成。应用一些新的合成方法和一种新型高效缩合剂, 简化了合成步骤, 提高了收率。