Нові фосфоровмісні поліциклічні сполуки із спіроаміногрупою

Aim. To synthesize hexahydrospiro[cyclopropane-1,10’-pyrido[1,2-c]quinazoline] and 2-λ5-benzo[f][1,4,2]diazaphosphepine derivatives – new N-P containing heterocyclic compounds with the 6-azaspiro[2.5]octane fragment.Results and discussion. A new analog of the powerful electrophilic reagent – “Alder dimer” ‒ was obtained from the interaction of triflic anhydride and spiro(4-cyclopropane) piperidinyl formamide, and further used to synthesize new Nʹ-PV- and PIII-substituted Νʹ-phenyl, Νʹʹ-hexahydro(azaspiro)octylformamidinium salts – precursors of acyclic N-phosphorylated diamino carbenes with a spiroamine group. It has been shown that acyclic N-phosphorylated diaminocarbenes are transient species affording various products. The structure of the final product is primarily determined by nature of the phosphorus-bearing substituent, namely a phosphoryl or phosphino-group. N-PV-substituted carbene undergoes a 1,2-phosphorus shift with the formation of (selenophosphoryl)formamidine in a high yield. For N-PIII-substituted carbene a compatible 1,3-H shift also occurs with the formation of an intermediate azomethine ylide converted into a new heterocyclic system – hexahydrospirocyclopropane -1,10’-pyrido[1,2-c]quinazoline. Under the action of acid an unexpected further expansion of the 6-member ring occurs with the formation of a diazepine derivative.Experimental part. The reaction of Alder reagent with N-PV-seleno phosphoryl arylamides afforded N-phosphorus substituted formamidinium salts, which are easily reduced to PIII analogues. In addition to the corresponding formamidines, the new N-phosphorylated spiroamine-containing polycyclic system was isolated from the reaction mixture formed by the deprotonation of such salts with a strong non-nucleophilic base.Conclusions. The Alder reagent approach allows synthesizing precursors of acyclic formamidine carbenes with the spiroamine group. Such carbenes are unstable. By converting these compounds N-PIII-substituted tetrahydropyrimidine and diazaphosphepine derivatives with the 6-azaspiro[2.5]octane fragment have been obtained for the first time.Мета. Синтезувати похідні  гексагідроспіро[циклопропан-1,10’-піридо[1,2-c]хіназоліну] та 2-λ5-бензо[f][1,4,2]діазафосфепіну – нові гетероциклічні N-Р-вмісні сполуки із фрагментом 6-азаспіро[2.5]октану. Результати та їх обговорення. У результаті взаємодії ангідриду трифлатної кислоти з формамідом (спіроциклопропан)піперидину отримано потужний електрофільний реагент – новий аналог «димера Альдера», за допомогою якого синтезовано нові Nʹ-РV- та РIII-заміщені солі Νʹ-феніл, Νʹʹ-азаспірооктил формамідинію – прекурсори ациклічних N-фосфорильованих діамінокарбенів зі спіроаміногрупою. Виявлено, що останні не є стабільними сполуками і зазнають in situ перетворень з утворенням різних продуктів, будова яких визначається насамперед типом фосфоровмісного замісника: фосфорильна або фосфіно-групи. N-PV-заміщений карбен зазнає 1,2-фосфорного зсуву з утворенням селенофосфорилформамідину з високим виходом. У N-PIII-заміщених карбенах відбувається також рівнобіжний 1,3-Н зсув з утворенням проміжного азометин іліду, який циклізується в нову гетероциклічну систему – гексагідроспіро[циклопропан-1,10’-піридо[1,2-c]- хіназолін]. Неочікуване подальше розширення 6-членного остову з утворенням похідної діазепіну відбувається під дією кислоти.Експериментальна частина. Оригінальною реакцією реактиву Альдера з N-селенофосфорил ариламідами одержано N-фосфорил заміщені формамідинові солі, які легко відновлюються до PIII-аналогів. Окрім відповідних формамідинів, нову N-фосфорильовану спіроаміновмісну поліциклічну систему було виділено з реакційної суміші, що утворюється за депротонування таких солей сильною ненуклеофільною основою. Висновки. Використання підходу з реактивом Альдера дозволяє синтезувати прекурсори ациклічних формамідинових карбенів зі спіроаміногрупою. Такі карбени є не стійкими. Перетворенням цих сполук уперше отримано N-PIII-заміщений тетрагідропіримідин та похідні 1,2,4-діазадигідрофосфепіну з фрагментом 6-азаспіро[2.5]октану.

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells

Neutral dinuclear gold(I) complexes with N-phosphanyl, N-heterocyclic carbenes (NHCPs)

Neutral dinuclear gold(I) complexes having general formula [Au2Cl2(NHCP)] (NHCP = N-phosphanyl N-heterocyclic carbene) have been synthesized by two different synthetic procedures: i) transmetalation of the NHCP ligand from the corresponding dinuclear silver(I) complex; ii) deprotonation of the corresponding N-phosphanyl azolium/tetrahydropyrimidinium salt in the presence of the gold(I) precursor. Interestingly, although the silver complexes are invariably dinuclear dicationic species of formula [Ag2(NHCP)2](OTf)2, both stoichiometries [Au2(NHCP)2](OTf)2 and [Au2Cl2(NHCP)] are potentially accessible with gold. Preference for either stoichiometry is dictated by the steric properties of the NHCP ligand as well as by a proper choice of the experimental conditions. On the other hand, preparation of copper(I) compounds with [Cu2Cl2(NHCP)] stoichiometry leads to product mixtures and has not led up to now to pure neutral compounds. Both the silver(I) and gold(I) complexes have been structurally characterized

Electrochemical Synthesis of Zirconium Pre-Catalysts for Homogeneous Ethylene Oligomerization

The catalytic activity of electrochemically synthesized zirconium carboxylates was studied in the process of ethylene oligomerization. Zirconium carboxylates were electrochemically synthesized directly from metallic zirconium and corresponding carboxylic acids (acetic, octanoic and lauric). A comprehensive study (element analysis, nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy, powder X-ray diffraction (PXRD)) of the synthesized zirconium carboxylates showed that these species contain bidentate carboxylate moieties. It was shown that obtained zirconium carboxylates, in combination with Et3Al2Cl3 (Al/Zr = 20), have a moderate activity of (7.6-9.9) × 103 molC2H4⋅molZr-1⋅h-1 in terms of ethylene oligomerization (at T = 80 ?C, p = 20 bar), leading to even-numbered C4-C10 linear alpha-olefins.1059-105

Cyclization of C-phosphorylated (P(III)) arylformamidines to 3H-1,3-benzazaphospholes

Marchenko A, Koidan H, Hurieva A, et al. Cyclization of C-phosphorylated (P(III)) arylformamidines to 3H-1,3-benzazaphospholes. Tetrahedron. 2011;67(40):7748-7758.A synthesis of 3H-1,3-benzazaphospholes starting from C-phosphorylated P(III) arylformamidines has been developed. Electron-donating substituents were found to enhance markedly the rate of the cyclization, with substituents at the meta position having the greatest effect. A plausible mechanism of the cyclization was proposed based on DFT calculations. (C) 2011 Elsevier Ltd. All rights reserved

Palladium(ii) complexes with chelating N-phosphanyl acyclic diaminocarbenes: Synthesis, characterization and catalytic performance in Suzuki couplings

Novel palladium(ii) complexes with the title ligands have been prepared and tested as precatalysts in Suzuki couplings of aryl chlorides.</p

Correction: Palladium(<scp>ii</scp>) complexes with chelating N-phosphanyl acyclic diaminocarbenes: synthesis, characterization and catalytic performance in Suzuki couplings

Correction for 'Palladium(ii) complexes with chelating N-phosphanyl acyclic diaminocarbenes: synthesis, characterization and catalytic performance in Suzuki couplings' by Anatoliy Marchenko et al., Dalton Trans., 2016, DOI: 10.1039/c5dt02250a