Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

General variable neighborhood search for the uncapacitated single allocation <Emphasis Type="Italic">p</Emphasis>-hub center problem

In this paper we propose a general variable neighborhood search heuristic for solving the uncapacitated single allocation p-hub center problem (USApHCP). For the local search step we develop a nested variable neighborhood descent strategy. The proposed approach is tested on benchmark instances from the literature and found to outperform the state-of-the-art heuristic based on ant colony optimization. We also test our heuristic on large scale instances that were not previously considered as test instances for the USApHCP. Moreover, exact solutions were reached by our GVNS for all instances where optimal solutions are known.     

Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase

Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants. Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases. Their stability is significantly influenced by N-glycosylation. However, yeast N-glycosylation pathways may synthesize plethora of N-glycan structures. A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1–EINV3). Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans. Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d -fructofuranoside (MF) synthesis. The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized. These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.     

Synthesis of New Phosphono Desmuramyldipeptide Analogs

Abstract

Muramyldipeptide (MDP) is the minimal bacterial cell wall moiety with imniunomodulating activity [I]. It is known that N-acetylglucosamine part is not essential lor immunomodulating activity and it can be replaced by phthalimido 01 adamantyl substituted side chains [2]. In our previous work we have modified the peptide backbone of phthaliniido-MDP analogs by introducing the phosphonamide 01 phosphinamide moiety at the end of the acyclic side chain or between Ala and Glu [3, 4]. We report the synthesis of phthalimido-MDP analog 2, where the o-carboxylic group of Glu is replaced by phosphonate moiety. Compound 1, which is orthogonally protected D,L-Abu(P), was prepared from benzyl 4-bromo-2-phthalimidobutyrate and triethyl phosphite. After removal of the phthalimide protecting group the obtained compound was coupled with Boc-L-Ah. Boc group was removed and the product was coupled with 5-phthalimidopentanoic acid to give 2. Both benzyl and ethyl protection can be selectively removed under mild conditions (catalytic hydrogenation. Nal).     

Carbon stable isotope composition of modern and archaeological Cornelian cherry fruit stones: a pilot study

The carbon stable isotope content of Cornelian cherry stones collected from wild tree stands in Serbia, SE Europe, was measured using elemental analyser-isotope ratio mass spectrometry, with the aim of recording natural carbon isotope composition of the fruit stones and its possible variation. The results show a significant variation in the carbon isotope values; we identified several environmental factors that, along with a number of other possible determinants, likely contributed to this variation. The obtained data are compared with the measurement of carbon isotope content of an archaeological specimen of Cornelian cherry stone discovered at the Neolithic site of Vin?a (ca. 5600–4500 BC) in Serbia. Notwithstanding the limitedness of the data and the complexity surrounding carbon fractionation and the isotopic variation, it is suggested that the differences/similarities in carbon isotope ratios between modern and archaeological Cornelian cherry stones, when measured for much larger assemblages, could potentially offer a glimpse into growing conditions of Cornelian cherry trees in the past.     

Isolation and X‐Ray Structures of Reactive Intermediates of Organocatalysis with Diphenylprolinol Ethers and with Imidazolidinones

Reaction of 2‐phenylacetaldehyde with the Me₃Si ether of diphenyl‐prolinol, with removal of H₂O, gives a crystalline enamine ( 1 ). The HBF₄ salts of the MePh₂Si ether of diphenyl‐prolinol and of 2‐(tert‐butyl)‐3‐methyl‐ and 5‐benzyl‐2,2,3‐trimethyl‐1,3‐imidazolidin‐4‐one react with cinnamaldehyde to give crystalline iminium salts 2, 3 , and 4 . Single crystals of the enamine and of two iminium salts, 2 and 3 , were subjected to X‐ray structure analysis (Figs. 1, 2, and 6), and a 2D‐NMR spectrum of the third iminium salt was recorded (Fig. 7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five‐membered heterocycles, i.e., D, E (Scheme 2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl‐prolinol derivatives (from the Cambridge File CSD; Table 1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig. 4). The iminium ions 3 and 4 are compared with N‐acylated imidazolidinones F and G (Figs. 9, 12, and 13, and Table 3), and common structural aspects such as minimalization of 1,5‐repulsion (the ‘A^1,3‐effect’), are discussed. The crystal structures of the simple diphenyl‐prolinol?HBF₄ salt (Fig. 3) and of Boc‐ and benzoyl‐(tert‐butyl)methyl‐imidazolidinone (Boc‐BMI and Bz‐BMI, resp.; Figs. 10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high‐level‐of‐theory DFT calculations (Figs. 5 and 8, and Table 2). Delicate details including pyramidalization of trigonal N‐atoms, distortions around iminium C?N bonds, shielding of diastereotopic faces, and the π‐interaction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations.