Prototropic behavior of cyclohexane substituted urethane and urea compounds. Observation of H-bond mediated 4HJH1H3 coupling constants across urea fragments

Two 1-aryl-3-cyclohexylurea and two 1-aryl-3-cyclohexylurethane with and without alkyl tail in aryl fragments were synthesized and their variable-temperature ¹H NMR spectra in chloroform, DMSO and DMF were recorded. The temperature dependences of chemical shift of NH protons for all compounds have been observed. The type of dependence has been explained by the aggregation of molecules and formation of ionic structures. The formation of intermolecular complexes leads to possible formation of symmetrical N1 ^{… …} H ^……N3 intramolecular hydrogen bond in urea fragment. As a result,^4hJ_H1H3 trans-hydrogen bond scalar coupling constants have been observed for the first time in low molecular weight compounds using a simple one-dimensional ¹H NMR experiment. The formation of strong intramolecular H-bond leads to π-conjugation not only with spacer but with phenyl ring too. It support the Gilli conception that RAHB formation is a result of π-electron delocalization. The presence in urea fragment of such kind interaction leads to formation of ionic structure, which has been detected by NMR and UV spectroscopies. The formation of ionic structure can explain the catalytic activity of such compounds and the mechanism of transformation in organic and bioorganic reactions in which involved the urea compounds.     

Out-cage metal ion coordination by novel benzoazacrown bisamides with carboxyl,pyridyl and picolinate pendant arms

A new series of macrocyclic diamides with carboxyl, pyridyl and picolinate pendant arms have been synthesized and the stability constants of their complexes with Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Pb²⁺ in water were determined. Complexes with a stoichiometry of 1 : 1 (M: L) were found for all ligands with the exception of 15-membered crown ethers with one pendant carboxyl or pyridine group. The ligand containing two picolinate backbone groups exhibits the highest values of the stability constants for all studied cations (logβ_ML?=?12.5–15.7). X-ray study of free ligands showed that the introduction of benzene and amide fragments into the macrocyclic moiety provides a flatten open structure of the ligand. The crystallographic analysis of Cu²⁺ and Zn²⁺ complexes revealed the external coordination of the metal atom by amine N atoms of the macrocycle and heteroatoms of the pendant groups.     

Hammerstein Integral Equations with Nontrivial Solutions

By means of critical point theory, existence theorems for nontrivial solutions to the Hammerstein equation x = KFx are given, where K is a compact linear integral operator and F is a nonlinear superposition operator. To this end, appropriate conditions on the spectrum of the linear parte are combined with growth and representation conditions on the nonlinear part to ensure the applicability of the mountain — pass lemma. The abstract existence theorems are applied to nonlinear elliptic equations and systems subject to Dirichlet boundary conditions.     

Sequential allylic C-H amination/vinylic C-H arylation: a strategy for unnatural amino acid synthesis from α-olefins

Tandem reaction sequences that selectively convert multiple C-H bonds of abundant hydrocarbon feedstocks to functionalized materials enable rapid buildup of molecular complexity in an economical way. A tandem C-H amination/vinylic C-H arylation reaction sequence is described under Pd(II)/sulfoxide-catalysis that furnishes a wide range of α- and β-homophenylalanine precursors from commodity α-olefins and readily available aryl boronic acids. General routes to enantiopure amino acid esters and densely functionalized homophenylalanine derivatives are demonstrated.     

Highly regiocontrolled Pd-catalyzed cross-coupling reaction of terminal alkynes and allenylphosphine oxides

The cross-coupling of a variety of terminal alkynes 1 with allenylphosphine oxides 2 catalyzed by a Pd(OAc)(2)-TDMPP system provided conjugated endo-enynes 3 solely, while the TCPC-catalyzed reaction of the same regents led to the exclusive formation of exo-isomers 4. The mechanistic rationale for these selective transformations was proposed. Synthetic usefulness of the prepared exo-enyne 4 was demonstrated in the synthesis of multisubstituted diarylbenzylphosphine oxides 5 via the Pd-catalyzed [4+2]-benzannulation reaction.     

Catalytic mechanism of yeast cytosine deaminase: an ONIOM computational study

The complete path for the deamination reaction catalyzed by yeast cytosine deaminase (yCD), a zinc metalloenzyme of significant biomedical interest, has been investigated using the ONIOM method. Cytosine deamination proceeds via a sequential mechanism involving the protonation of N(3), the nucleophilic attack of C(4) by the zinc-coordinated hydroxide, and the cleavage of the C(4)-N(4) bond. The last step is the rate determining step for the generation of the zinc bound uracil. Uracil is liberated from the Zn atom by an oxygen exchange mechanism that involves the formation of a gem-diol intermediate from the Zn bound uracil and a water molecule, the C(4)-O(Zn) cleavage, and the regeneration of the Zn-coordinated water. The rate determining step in the oxygen exchange is the formation of the gem-diol intermediate, which is also the rate determining step for the overall yCD-catalyzed deamination reaction.     

Divergent C-H functionalizations directed by sulfonamide pharmacophores: late-stage diversification as a tool for drug discovery

Modern drug discovery is contingent on identifying lead compounds and rapidly synthesizing analogues. The use of a common pharmacophore to direct multiple and divergent C-H functionalizations of lead compounds is a particularly attractive approach. Herein, we demonstrate the viability of late-stage diversification through the divergent C-H functionalization of sulfonamides, an important class of pharmacophores found in nearly 200 drugs currently on the market, including the non-steroidal anti-inflammatory blockbuster drug celecoxib. We developed a set of six categorically different sulfonamide C-H functionalization reactions (olefination, arylation, alkylation, halogenation, carboxylation, and carbonylation), each representing a distinct handle for further diversification to reach a large number of analogues. We then performed late-stage, site-selective diversification of a sulfonamide drug candidate containing multiple potentially reactive C-H bonds to synthesize directly novel celecoxib analogues as potential cyclooxygenase-II (COX-2)-specific inhibitors. Together with other recently developed practical directing groups, such as CONHOMe and CONHC(6)F(5), sulfonamide directing groups demonstrate that the auxiliary approach established in asymmetric catalysis can be equally effective in developing broadly useful C-H activation reactions.