Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity.

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH3. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.

Photochemically Induced Dynamic Nuclear Polarization of Heteronuclear Singlet Order.

Photochemically induced dynamic nuclear polarization (photo-CIDNP) is a method to hyperpolarize nuclear spins using light. In most cases, CIDNP experiments are performed in high magnetic fields and the sample is irradiated by light inside a nuclear magnetic resonance (NMR) spectrometer. Here we demonstrate photo-CIDNP hyperpolarization generated in the Earth's magnetic field and under zero- to ultralow-field (ZULF) conditions. Irradiating a sample containing tetraphenylporphyrin and para-benzoquinone for several seconds with light-emitting diodes produces strong hyperpolarization of 1H and 13C nuclear spins, enhancing the NMR signals more than 200 times. The hyperpolarized spin states at the Earth's field and in ZULF are different. In the latter case, the state corresponds to the singlet order between scalar-coupled 1H-13C nuclear spins. This state has a longer lifetime than the state hyperpolarized at Earth's field. The method is simple and cost-efficient and should be applicable to many molecular systems known to exhibit photo-CIDNP, including amino acids and nucleotides.

aza-Wittig Reaction with Nitriles: How Carbonyl Function Switches from Reacting to Activating.

Transformations of α-EWG-substituted (electron-withdrawing group, EWG) γ-azidobutyronitriles proceeding via unusual aza-Wittig reactions between the phosphazene and nitrile functions and affording pyrrole-derived iminophosphazenes were developed. α-EWGs were found to control chemoselectivity and, depending on their nature, act as CN group activators (e.g., ester, amide, or nitrile) or competitors (e.g., ketone) in aza-Wittig reactions. To demonstrate the synthetic utility of the obtained iminophosphazenes as N, N-binucleophiles, their transformations into pyrrole-fused systems, pyrrolo[1,2- a]imidazoles and pyrrolo[1,2- a][1,3]diazepines, were carried out.

Elimination of signals tilting caused by B0 field inhomogeneity using 2D-lineshape reference deconvolution.

An efficient approach for reference deconvolution of two-dimensional spectra aiming at the correction of static field inhomogeneity was established. In comparison to known techniques, a great improvement was achieved using the cross-section along the diagonal of the reference peak instead of its full 2D line shape. The method is termed pseudo-2D diagonal deconvolution. The approach developed allows suppressing the two-dimensional peaks tilting caused by the magnetic field inhomogeneity, while keeping the signal-to-noise ratio constant. Long-known method of 2D reference deconvolution (true-2D reference deconvolution) was also applied for comparison. The neutral and resolution-enhancing pseudo-2D deconvolutions were successfully applied for the resolution of complex overlapping multiplets and for measuring small scalar coupling constants. The new algorithm for the elimination of shape distortion of two-dimensional peaks showed to be promising in the perspective of an automated analysis of 2D correlation NMR spectra.

Copper(I)-Catalyzed Cycloaddition of Azides to Multiple Alkynes: A Selectivity Study Using a Calixarene Framework.

Copper(I)-catalyzed addition of limited amounts of azides to multiple alkynes, which led to statistical mixtures of triazole/acetylene derivatives or, in other cases, resulted in preferred formation of multiple triazoles, was studied at pre-organizable calixarene platforms bearing up to four propargyl groups. Depending on calixarene structures and reaction conditions, the unprecedented specific or selective formation of exhaustively triazolated calixarenes or a complete loss of the selectivity were observed. Both autocatalytic copper activation and a local copper(I) concentration increase due to copper-triazole complexation were thoroughly studied as the most expected reasons for the selectivity and both were disproved. Mixed triazolated/propargylated calixarenes and their copper(I) complexes proved not to be involved in the cascade-like process that was modeled to be driven by an intramolecular transfer of two copper(I) ions from a just-formed binuclear copper intermediate to the adjacent acetylene unit.

Calix[4]tubes: an approach to functionalization.

Adamantylcalix[4]arenes decorated with ester groups and calix[4]arene tetratosylates were used to prepare a series of calix[4]tubes bearing 3-methoxycarbonyl- and 3-methoxycarbonylmethyl-1-adamantyl units (up to eight) in good yield. These compounds were subjected to further chemical transformations giving a wide set of novel ester-, acid-, hydroxy-, amine-, and urea-functionalized calix[4]tubes. Introduction of urea groups into the calixtube core led not only to anion-targeted receptors, but also provided heteroditopic behavior of the hosts, which enriches the well-established potassium-uptake ability of calix[4]tubes.

Furan ring opening-pyrrole ring closure: a new synthetic route to aryl(heteroaryl)-annulated pyrrolo[1,2-a][1,4]diazepines.

A method of synthesis of pyrrolo[1,2-a][1,4]benzodiazepines is described. This method is based on the recyclization of N-(furfuryl)anthranilamides under treatment with an aq. HCl/AcOH system and allows one to form both diazepine and pyrrole rings in one step. The reaction proceeds via furan ring opening into a diketone moiety followed by consecutive interaction of the NH(2)-group with both carbonyl functions. The process is not efficient in the presence of alkyl or aryl groups on amide nitrogen due to competitive furfuryl cation elimination. But alkylation of pyrrolo[1,2-a][1,4]benzodiazepines yields efficiently the corresponding N-alkyl derivatives. Steric effects also prevent cyclization due to reversibility of diazepine ring formation under these reaction conditions. However, the corresponding pyrrolo[1,2-a][1,4]benzodiazepines can be obtained by a stepwise process, i.e., 1) furan ring opening with aq. HCl/AcOH and 2) cyclization of isolated aminodiketones under treatment with glacial acetic acid. Another efficient procedure for the synthesis of pyrrolo[1,2-a][1,4]benzodiazepines consists of acid-catalyzed furan ring opening of N-(furfuryl)-2-nitrobenzamides followed by treatment of the formed nitrodiketone with Fe/AcOH. It leads to a one pot reduction of nitro group to amine, cyclization into diazepine and pyrrole ring formation. This procedure is efficient both for substrates with steric demands and for N-alkyl- or N-aryl-N-(furfuryl)amides. The proposed approach can be also applied to the synthesis of parent pyrrolo[1,2-a][1,4]diazepines or their analogues annulated to heterocycles.