Synthesis and Characterization of Three-Coordinate Ni(III)-Imide Complexes

A new family of low-coordinate nickel imides supported by 1,2-bis(di-tert-butylphosphino)ethane was synthesized. Oxidation of nickel(II) complexes led to the formation of both aryl- and alkyl-substituted nickel(III)-imides, and examples of both types have been isolated and fully characterized. The aryl substituent that proved most useful in stabilizing the Ni(III)-imide moiety was the bulky 2,6-dimesitylphenyl. The two Ni(III)-imide compounds showed different variable-temperature magnetic properties but analogous EPR spectra at low temperatures. To account for this discrepancy, a low-spin/high-spin equilibrium was proposed to take place for the alkyl-substituted Ni(III)-imide complex. This proposal was supported by DFT calculations. DFT calculations also indicated that the unpaired electron is mostly localized on the imide nitrogen for the Ni(III) complexes. The results of reactions carried out in the presence of hydrogen donors supported the findings from DFT calculations that the adamantyl substituent was a significantly more reactive hydrogen-atom abstractor. Interestingly, the steric properties of the 2,6-dimesitylphenyl substituent are important not only in protecting the Ni═N core but also in favoring one rotamer of the resulting Ni(III)-imide, by locking the phenyl ring in a perpendicular orientation with respect to the NiPP plane

The synthesis and characterization of polypeptide-adriamycin conjugates and its complexes with adriamycin. Part I

Poly(α-l-glutamic acid) (PGA) was grafted with amino acid and oligopeptide spacers up to 5 amino acids with the use of N,N'-carbonyldiimidazole and 2,3-dihydro-1,2-benz-isothiazole-3-on-1, 1-dioxide (saccharin) as an additive, and these polypeptides were characterized. The antitumor antibiotic adriamycin was covalently coupled via an amide bond onto PGA and onto the grafted polymers with the use of N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ); these conjugates were characterized. The conjugates containing Gly—Gly—l-Leu spacer arms did yield free adriamycin upon digestion with papain. Adriamycin gave fairly stable complexes with PGA—adriamycin and branched poly peptide—adriamycin conjugates; these complexes were characterized

1,3-Dipolar cycloadditions of azomethine imines

Azomethine imines are considered 1,3-dipoles of the aza-allyl type which are transient intermediates and should be generated in situ but can also be stable and isolable compounds. They react with electron-rich and electron-poor olefins as well as with acetylenic compounds and allenoates mainly by a [3 + 2] cycloaddition but they can also take part in [3 + 3], [4 + 3], [3 + 2 + 2] and [5 + 3] with different dipolarophiles. These 1,3-dipolar cycloadditions (1,3-DC) can be performed not only under thermal or microwave conditions but also using metallo- and organocatalytic systems. In recent years enantiocatalyzed 1,3-dipolar cycloadditions have been extensively considered and applied to the synthesis of a great variety of dinitrogenated heterocycles with biological activity. Acyclic azomethine imines derived from mono and disubstituted hydrazones could be generated by prototropy under heating or by using Lewis or Brønsted acids to give, after [3 + 2] cycloadditions, pyrazolidines and pyrazolines. Cyclic azomethine imines, incorporating a C–N bond in a ring, such as isoquinolinium imides are the most widely used dipoles in normal and inverse-electron demand 1,3-DC allowing the synthesis of tetrahydro-, dihydro- and unsaturated pyrazolo[1,5-a]isoquinolines in racemic and enantioenriched forms with interesting biological activity. Pyridinium and quinolinium imides give the corresponding pyrazolopyridines and indazolo[3,2-a]isoquinolines, respectively. In the case of cyclic azomethine imines with an N–N bond incorporated into a ring, N-alkylidene-3-oxo-pyrazolidinium ylides are the most popular stable and isolated dipoles able to form dinitrogen-fused saturated and unsaturated pyrazolopyrazolones as racemic or enantiomerically enriched compounds present in many pharmaceuticals, agrochemicals and other useful chemicals.We acknowledge continued financial support from the Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, and CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P, CTQ2014-51912-REDC, and CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), and the University of Alicante

Photochemistry of N-(selenoalkyl)-phthalimides. Formation of N, Se-heterocyclic systems

A variety of N-(selenomethyl)alkyl-phthalimides (alkyl = -(CH2)n-; n = 2-5, 1a, b, d, e) and N-(selenobenzyl)propyl phthalimide (1c) were synthesized and their photochemistry was studied at λ = 300 nm. Steady-state photolysis and laser time-resolved spectroscopy studies confirmed that these reactions proceeded by direct or acetone-sensitized excitation followed by intramolecular electron transfer (ET) between Se atom and the phthalimide moiety. Two main pathways are possible after ET: proton transfer to the ketyl radical anion from the CH3Se+ or the -CH2Se+- moieties, yielding the corresponding biradicals. Collapse of these biradicals yields cyclization products with the respective endo or exo selenium-containing heterocycles. Competition between both proton transfer processes depends on the chain length of the alkyl spacer between the phthalimide and Se groups as well as the size of the cycle being formed.Fil: Oksdath Mansilla, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Heredia, Adrián Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Argüello, Juan Elias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Peñeñory, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Sonogashira/N-acyliminium ion aromatic π-cyclisation processes: access to tetra- and pentacyclic lactams

Application of the Sonogashira reaction of N-alkynylimides with 2-iodophenol or 2-iodo-N-tosylaniline affords 2-(N-alkylimino)-benzofurans and indoles in good yield. Selective partial reduction of the latter followed by treatment with TsOH generates N-acyliminium ions, which cyclise to afford tetra- and pentacyclic lactams in good yield. The latter are reduced to the analogous cyclic amines by BH3

Reduction of some cyclic derivatives of diphenic acid with sodium borane in alcohols

Reduction of heptamerous cyclic imides with sodium borane has been carried out for the first time by the example of some imides of diphenic acid. In this case for the first time amides of 2'-hydroxymethylxenyl-2-carboxylic acid which are potentially valued bioactive compounds were obtained. It was shown that the nature of substituent at nitrogen atom influences the reaction products yields and composition. The reduction of diphenic acid anhydride with sodium borane in simple alcohols occurs with the formation of reduction products - 7H-dibenzyl[c,e] oxepin-5-on (36...46 %) as well as products of diphenic acid alcoholysis-monoester (29...36 %). In this case the nature of alcohol influences weakly reaction products rati

Network-analysis-guided synthesis of weisaconitine D and liljestrandinine.

General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three families of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites

5,6-Dihydro-2H-pyran-3(4H)-on als Baustein zur Synthese pyrananellierter Heterocyclen

Während 5,6-Dihydro-2H-pyran-3(4H)-on (3) sich mit ortho-substituierten Phenylcarbonylverbindungen nur in Einzelfällen regioselektiv zu pyrananellierten Heterocyclen umsetzt - z. B. zum Pyrano[2,3-b]chinolin 7c -, gelingt das besser mit dem aus 3 hergestellten Enamin 15d, dem Silylenolether 18 und dem daraus gewonnenen Lithiumenolat 14. Diese Pyranderivate mit 2,3-oder 3,4-Doppelbindungen eignen sich zur gezielten Darstellung von 2- oder 4-substituierten 3-Pyranonen - z.B. 2, 21a, 21b, 23a-c, 26a-c, 31a-c, 32, sowie 35a-c - und von Pyrano[3,2-b]- oder -[3,4-b]chinolinen, -chinolonen, -chromonen und -thiochromonen 6a, 30a-c und 38a-d