Rhodium‐Catalyzed Homogeneous Reductive Amidation of Aldehydes

The catalytic reductive amidation of an aldehyde (hexanal) with an amide (acetamide) is reported. Apart from the desired N‐hexylacetamide, the two isomeric unsaturated intermediates as well as hexanol are produced together with higher mass products that arise from aldol condensation and diamide coupling of the aldehyde. Screening of different catalyst precursor salts, ligands and reaction conditions led to the finding that the catalytic system based on the (cyclooctadiene)rhodium chloride dimer, [Rh(cod)Cl]₂, in combination with the ligand xantphos and an acid co‐catalyst results in high selectivity for the desired product. Under optimized conditions nearly full conversion is reached with high selectivity to the desired N‐alkylamide and with a very high N ‐ alkylamide/alcohol ratio, while producing only small amounts of by‐products. The scope of the reaction has been investigated using different amides as well as aldehydes; the results show the general applicability of this novel reaction, but with electron‐withdrawing amides the selectivity to N‐alkylamide is lower. NMR studies showed that the nucleophilic addition of acetamide to hexanal is acid catalyzed, forming N‐(1‐hydroxyhexyl)acetamide in equilibrium with both hexanal and the dehydrated unsaturated imides. A catalytic mechanism is proposed in which a strong acid such as HOTs acts as a co‐catalyst by establishing a rapid chemical equilibrium between the aldehyde, acetamide and the intermediates. Furthermore, it is proposed that the presence of acid causes a change in catalytic species, enabling a cationic Rh/xantphos hydrogenation catalyst to selectively hydrogenate the intermediates to N‐hexylacetamide in the presence of hexanal.     

Rapid and Green Analytical Method for the Determination of Quinoline Alkaloids from Cinchona succirubra Based on Microwave-Integrated Extraction and Leaching (MIEL) Prior to High Performance Liquid Chromatography

Quinas contains several compounds, such as quinoline alkaloids, principally quinine, quinidine, cinchonine and cichonidine. Identified from barks of Cinchona, quinine is still commonly used to treat human malaria. Microwave-Integrated Extraction and Leaching (MIEL) is proposed for the extraction of quinoline alkaloids from bark of Cinchona succirubra. The process is performed in four steps, which ensures complete, rapid and accurate extraction of the samples. Optimal conditions for extraction were obtained using a response surface methodology reached from a central composite design. The MIEL extraction has been compared with a conventional technique soxhlet extraction. The extracts of quinoline alkaloids from C. succirubra obtained by these two different methods were compared by HPLC. The extracts obtained by MIEL in 32 min were quantitatively (yield) and qualitatively (quinine, quinidine, cinchonine, cinchonidine) similar to those obtained by conventional Soxhlet extraction in 3 hours. MIEL is a green technology that serves as a good alternative for the extraction of Cinchona alkaloids.     

Experimental and modelling of supercritical oil extraction from rapeseeds and sunflower seeds

The supercritical oil extraction from oleaginous seeds (sunflower and rapeseeds) is presented here through experimental and modelling results. The experimental setup allows an accurate following of the mass of the oil extracted and to derive the experimental influences of pressure, temperature and supercritical CO₂ flowrate on the extraction curves. These parameters are very sensitive and highlight the necessity of precise optimisation of experimental conditions. In order to complete the behaviour of supercritical fluids extraction, an improved modelling is proposed. The modelling basic equations are based on others modelling published previously. In this work, the determination of several parameters comes from correlations and the other constants are fitted with all the experimental results. Thus the modelling is more representative and predictive as other ones. The modelling results present a good agreement with the experimental results, and hence it can be used for the dimensioning of some extraction autoclaves.     

Metabolic Effects of Krill Oil are Essentially Similar to Those of Fish Oil but at Lower Dose of EPA and DHA,in Healthy Volunteers

The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.     

Selective Production of 2-Phenylhexane from Benzene and <Emphasis Type="Italic">n</Emphasis>-Hexane Over Pt- and Ga-Modified Zeolites

Abstract  

Alkylation of benzene with n-hexane was performed over H-ZSM-5 and monometallic Ga- and Pt- and bimetallic Ga- and Pt-modified ZSM-5. The influence of the particle size and the method of incorporation of Ga (during hydrothermal synthesis, by solid-state ion exchange, or by liquid-state ion exchange) was determined. The presence of Pt and well-dispersed extraframework Ga in H-ZSM-5 increased the selectivity in alkylation and suppressed cracking reactions. Well-dispersed Pt particles led to better catalytic performance. The method of Ga incorporation played an important role in obtaining higher selectivity to alkylation products and in the suppression of side reactions. Up to 93% selectivity in alkylation (of which >95% was to 2-phenylhexane) was reached over 2 wt% Pt/H-Ga^fZSM5, in which Ga occupied framework positions. We propose that the close proximity of very small Pt nanoparticles and Ga–(OH)–Si acid sites results in the optimal bifunctional catalyst for selective production of 2-phenylhexane from benzene and n-hexane. During the reaction, the catalyst deactivated, most probably due to the sintering of the Pt particles.     

Synthesis and biological investigation of novel tricyclic benzodiazepinedione-based RGD analogues

Integrins, a widely expressed family of heterodimeric cell surface adhesion proteins, are expressed in a variety of cell types. They play a decisive role in cell-cell adhesion or cell to extracellular matrix adhesion events. Antagonists of alpha(v)beta(3) or alpha(IIb)beta(3) integrin may have a potential use in suppression of pathological processes. We present the synthesis of novel tricyclic benzodiazepinedione-based RGD analogues, which were subsequently tested in a solid-phase receptor assay in order to investigate their binding affinities towards alpha(v)beta(3) and alpha(IIb)beta(3) integrin.     

Low molecular weight oligo-β-hydroxybutyric acids and 3-hydroxy-N-phenethyl-butyramide – new products from microorganisms

Summary A new group of low-molecular weight channel-forming oligo(hydroxybutyric acids) (cPHBs, 1 with n = 8–30; main component MW ≈ 1300 dalton) was isolated from microorganisms of different origin. Inclusion bodies were electron-microscopically visible in cells in the state of autolysis, not in cells in the exponential phase of growth. cPHB and high-molecular poly(l3-hydroxybutyric acid) (sPHB) is cleaved by phenylethylamine and forms the corresponding monomeric hydroxybutyramide and – under drastic conditions, the crotylamide. One of these compounds, the 3-hydroxy-N-phenethyl-butyramide (5), was isolated as a new natural product now. Received: 28 March 2002/Revised version: 26 July 2002/ Accepted: 26 July 2002 RID="*" ID="*"Marine Bakterien, XVII. XVI: R.P. Maskey, R.N. Asolkar, E. Helmke, and H. Laatsch, Chalcomycin B, a new antibiotic from a marine Streptomyces sp. B7064. J. Antibiot., submitted 2002 Correspondence to Hartmut Laatsch, e-mail: hlaatsc@gwdg.de, Fax: +49-551-399660     

Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.