bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives
Authors: Wu Bian , Szymanski Wiktor , Wietzes Piet , de Wildeman Stefaan , Poelarends Gerrit J. , Feringa Ben L. , Janssen Dick B. 
Published: January 2009

AbstractThe phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of α‐phenylalanine to β‐phenylalanine, an important step in the biosynthesis of the N‐benzoyl phenylisoserinoyl side‐chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)‐cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring‐substituted (E)‐cinnamic acids can serve as a substrate in PAM‐catalysed ammonia addition reactions for the biocatalytic production of several important β‐amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non‐natural aromatic α‐ and β‐amino acids in excellent enantiomeric excess (ee >99 %). The internal 5‐methylene‐3,5‐dihydroimidazol‐4‐one (MIO) cofactor is essential for the PAM‐catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.
Regio‐, Peri‐, and Torquoselectivity in Hydroxy Heptatrienyl Cation Electrocyclizations: The Iso/Homo‐Nazarov Reaction
Authors: Faza Olalla Nieto , López Carlos Silva , Álvarez Rosana , de Lera Ángel R. 
Published: January 2009

AbstractCompetition: The electrocyclizations of 1‐ and 3‐hydroxyheptatrienyl cations (see scheme) have been computationally studied at the B3LYP/6‐311G(d) level. The 1‐hydroxy system clearly favors a 4e−over a 6e−process, while for the 3‐hydroxy isomer these mechanisms compete.magnified imageThe electrocyclizations of 1‐ and 3‐hydroxyheptatrienyl cations have been computationally studied at the B3LYP/6‐311G(d) level. The 1‐hydroxy system clearly favors a 4πe−over a 6πe−process, while for the 3‐hydroxy isomer these mechanisms compete. Substituents can either enhance or invert this periselectivity through steric or electronic effects, respectively. Houk's model of torquoselectivity helps to explain the activation energy differences between the alternative 4πe−electrocyclizations available for each system. The cyclopentenyl cations thus obtained can evolve, either through intramolecular trapping by the vinyl group or by 1,3‐proton migration, along reaction coordinates which could correspond to either very asynchronous concerted mechanisms, or two‐step reactions with very shallow or non‐existent intermediates.
Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families
Authors: Cardona Francesca , Parmeggiani Camilla , Faggi Enrico , Bonaccini Claudia , Gratteri Paola , Sim Lyann , Gloster Tracey M. , Roberts Shirley , Davies Gideon J. , Rose David R. , Goti Andrea 
Published: January 2009

AbstractSelective glucosylation: Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6‐O‐α‐glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes.magnified imageTotal synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6‐O‐α‐glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao–Fleming oxidation and selective α‐glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.
Density Functional Study of Proline‐Catalyzed Intramolecular Baylis–Hillman Reactions
Authors: Duarte Filipe J. S. , Cabrita Eurico J. , Frenking Gernot , Santos A. Gil 
Published: January 2009

AbstractA rationalization of stereoselectivity: The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path (see scheme).magnified imageThe mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods at the B3LYP/6‐31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6‐31++G(d,p)//B3LYP/6‐31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co‐catalyst, water is still important in the imidazole addition step, but is not present in the Baylis–Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis–Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.
Stereoselective Allylation of Ketones: Explanation for the Unusual Inversion of the Induced Stereochemistry in the Auxiliary‐Mediated Crotylation and Pentenylation of Butanone by DFT Calculations
Authors: Tietze Lutz F. , Kinzel Tom , Schmatz Stefan 
Published: January 2009

AbstractThe solvent makes the difference: While attack at the Re face of the intermediate oxocarbenium ion becomes less energy demanding with increasing size of R′, it is the solvent effect that makes this attack the main trajectory, leading to inversed stereochemistry (see picture).magnified imageAuxiliary‐mediated domino crotylations and pentenylations of butanone yield homoallylic ethers with two newly formed stereogenic centers. With our norpseudoephedrine‐derived auxiliary, we observed the formation of anti isomers exclusively, and the nature of the major isomer was independent of the substrate double bond geometry. Interestingly, there is a switch in induced selectivity when going from crotylation to pentenylation. Here, we present the computational rationalization for this behavior by identification of the relevant transition states (TSs), the energies of which were determined by using the B3LYP/6‐31+G(d) level of theory in combination with the PCM/UAKS method to include the effects exerted by the solvent dichloromethane. To quickly narrow down the number of potentially relevant TSs from the whole set of 288 and 864 TSs for the crotylation and pentenylation, respectively, we employed a screening process based on B3LYP//AM1 energies. The predicted selectivities are in good agreement with experimentally determined ones. Furthermore, the obtained results also facilitate an explanation of the selectivities obtained in hexenylations and heptenylations. Finally, activation energies were determined that account for the significantly longer reaction times than those for the domino allylation with unsubstituted trimethylallylsilane.
High serum des‐gamma‐carboxy prothrombin level predicts poor prognosis after radiofrequency ablation of hepatocellular carcinoma
Authors: Kobayashi Masahiro , Ikeda Kenji , Kawamura Yusuke , Yatsuji Hiromi , Hosaka Tetsuya , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Kumada Hiromitsu 
Published: January 2009

AbstractBACKGROUND:Currently, surgical resection is considered the first‐line treatment for early stage hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) has been an alternative choice for unresectable HCC. However, RFA is expected to have similar therapeutic efficacy for early stage HCC with fewer invasions.METHODS:The authors retrospectively analyzed 199 patients who underwent surgery and 209 patients who underwent RFA for HCC with a maximum diameter of ≤3 cm and tumors numbering ≤3. All patients were complicated with Child‐Pugh A cirrhosis.RESULTS:The 3‐ and 5‐year survival rates of the resection (90.3%, 79.0%, respectively) and RFA groups were similar (87.4%, 74.8). The 1‐ and 3‐year tumor recurrence‐free survival rates of the resection group (83.1%, 51.0%, respectively) were higher than in the RFA group (82.7%, 41.8%;P= .011). Multivariate analysis identified prothrombin time ≥80% (hazard ratio [HR], 2.72; 95% confidence interval [CI], 1.56‐4.74;P< .001) as an independent prognostic factor for survival in the resection group. Des‐gamma‐carboxy prothrombin (DCP) <100 arbitrary units (AU)/L (HR, 5.49; CI, 2.23‐13.5;P< .001) and platelet count ≥1.0 × 105(HR, 2.70; CI, 1.24‐5.88;P= .012) were significant markers in the RFA group. Among patients with DCP ≥100 AU/L, treatment procedure (HR, 1.26; CI, 1.04‐1.53;P= .020) was a significant prognostic factor for survival.CONCLUSIONS:High DCP levels reflect the biologic aggressiveness and progression of HCC tumors. In the aforementioned cases, we recommend surgical resection rather than RFA for such patients. Cancer 2009. © 2008 American Cancer Society.
Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer
Authors: Bellone Stefania , Anfossi Simone , O'Brien Timothy J. , Cannon Martin J. , Silasi Dan‐Arin , Azodi Masoud , Schwartz Peter E. , Rutherford Thomas J. , Pecorelli Sergio , Santin Alessandro D. 
Published: January 2009

AbstractBACKGROUND:Tumor‐associated differentially expressed gene‐12 (TADG‐12) is a serine protease recently found highly differentially expressed in epithelial ovarian cancer. The goal of this study was to identify potential immunogenic peptides derived from TADG‐12 for immunotherapy of ovarian carcinoma.METHODS:A bioinformatics approach (ie, the BIMAS algorithm, National Institutes of Health, http://bimas.dcrt.nih.gov/molbio/hla_bind) was used to identify multiple immunogenic peptides derived from TADG‐12 that bind to human leukocyte antigen‐A2.1 and elicit peptide‐specific human cytotoxic T lymphocyte (CTL) responses in healthy individuals and in patients with advanced stage ovarian cancer.RESULTS:CD8+ CTL populations generated against 5 TADG‐12–derived peptides were consistently able to induce lysis of autologous peptide‐loaded target cells above background. Importantly, TADG‐12 YLPKSWTIQV peptide‐specific CTLs from healthy donors and ovarian cancer patients were found to effectively kill ovarian cancer cells naturally expressing TADG‐12. Cytotoxicity was significantly inhibited by anti–human lymphocyte antigen (HLA)‐A2.1 (BB7‐2) and anti–HLA class I (W6 of 32) monoclonal antibodies, whereas natural killer–sensitive K562 cells were not lysed. TADG‐12 YLPKSWTIQV peptide‐specific CTL precursor frequency was low in peripheral blood leukocytes of normal donors and ovarian cancer patients, as determined by interferon‐γ production in enzyme‐linked immunosorbent spot‐forming cell assays. Intracellular cytokine expression measured by flow cytometry after OKT‐3 monoclonal antibody stimulation showed a type 1 cytokine profile in YLPKSWTIQV peptide‐specific CTLs.CONCLUSIONS:The TADG‐12 YLPKSWTIQV peptide is an immunogenic epitope in ovarian tumors and may represent an attractive target for immunotherapy of ovarian cancer. These data may pave the way for TADG‐12 peptide‐derived cell‐based therapy, including dendritic cell immunotherapy, for the vaccination of ovarian cancer patients harboring chemotherapy‐resistant or residual disease. Cancer 2009. © 2008 American Cancer Society.
Phase 1 study of an oxaliplatin and etoposide regimen in pediatric patients with recurrent solid tumors
Authors: McGregor Lisa M. , Spunt Sheri L. , Santana Victor M. , Stewart Clinton F. , Ward Deborah A. , Watkins Amy , Laningham Fred H. , Ivy Percy , Furman Wayne L. , Fouladi Maryam 
Published: January 2009

AbstractBACKGROUND:The combination of a platinating agent and etoposide has induced responses in various pediatric tumors. The study estimated the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors.METHODS:Oxaliplatin was administered on Day 1 and etoposide on Days 1 to 3 of each 21‐day course. Cohorts of 3 to 6 patients were enrolled at 3 dose levels: 1) oxaliplatin at a dose of 130 mg/m2 and etoposide at a dose of 75 mg/m2, 2) oxaliplatin at a dose of 130 mg/m2 and etoposide at a dose of 100 mg/m2, and 3) oxaliplatin at a dose of 145 mg/m2 and etoposide at a dose of 100 mg/m2. Calcium and magnesium infusions were used at dose level 3 in an attempt to escalate the oxaliplatin dose past the single‐agent MTD.RESULTS:The 16 patients received a total of 63 courses. At dose level 1, dose‐limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose‐limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4 patients experienced dose‐limiting neutropenia; none experienced grade 3 or 4 acute neuropathy. Six patients required prolongation of the oxaliplatin infusion because of acute sensory neuropathy. Responses were observed in patients with medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3 others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma had prolonged disease stabilization.CONCLUSIONS:The MTD of this regimen was found to be oxaliplatin at a dose of 130 mg/m2 given on Day 1 and etoposide at a dose of 100 mg/m2/d given on Days 1 to 3. Neutropenia was found to be the DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin dose. The combination was well‐tolerated and demonstrated antitumor activity. Cancer 2009. © 2008 American Cancer Society.
Bendamustine
Authors: Kalaycio Matt 
Published: January 2009

AbstractAlkylating agents form the basis of most combination treatment regimens for low‐grade lymphoproliferative disorders. Bendamustine is a unique alkylating agent that has distinctive preclinical activity in cell lines resistant to other alkylators. Furthermore, clinical activity has been demonstrated in patients with alkylating agent resistant disease. Recently, larger studies have been organized to study the clinical effects of bendamustine further. In indolent B‐cell non‐Hodgkin lymphoma that is resistant to rituximab, bendamustine induced a remission in 77% of patients. Myelosuppression was identified as the most common toxicity. In 2 studies of similar populations of patients, the combination of bendamustine and rituximab induced remission 90% of patients with a median progression‐free survival of 23‐24 months. The overall remission rate was 59% in a prospective, randomized study of untreated patients with chronic lymphocytic leukemia, which was significantly greater than the rate of 26% in the chlorambucil control arm (P < 0.001). Combined with rituximab, bendamustine induces a remission in 67% of patients with relapsed or refractory chronic lymphocytic leukemia. Bendamustine is an active agent for the treatment of low‐grade lymphoproliferative disorders and more study is needed to determine which dose and schedule is optimal, and which patients will derive the greatest benefit from its use. Cancer 2009. © 2008 American Cancer Society.
Early changes in tumor size in patients treated for advanced stage nonsmall cell lung cancer do not correlate with survival
Authors: Birchard Katherine R. , Hoang Jenny K. , Herndon James E. , Patz Edward F. 
Published: January 2009

AbstractBACKGROUND:In clinical trials, change in tumor size is used to stratify patients into response categories. The objective of the current study was to: 1) determine whether early change in the tumor size were correlated with survival in patients with advanced nonsmall cell lung cancer (NSCLC) using modified response categories from the Response Evaluation Criteria in Solid Tumors (RECIST), and 2) to determine whether there was an optimal percentage change in tumor size that could be used to define a partial response that also correlated with survival.METHODS:A total of 99 consecutive patients presenting for the treatment of advanced NSCLC during the year 2003 who had computed tomography (CT) scans before and after treatment available for review were included in the study. The largest target thoracic lesion was measured on CT before treatment, and again 2 months to 3 months after the initiation of treatment. Percent change in tumor size was calculated. The relation between tumor response and patient survival was investigated.RESULTS:There was no definite relation noted between early tumor response and patient survival (P = .754). Patients who had any initial reduction in tumor size were not found to have a significantly different survival compared with patients with initial disease progression (P = .580). In addition, there was no particular percent reduction in tumor size that was found to optimally correlate with survival.CONCLUSIONS:There is no evidence of a relation between early changes in tumor size and survival among patients with advanced stage NSCLC. To predict survival in patients with advanced NSCLC, response criteria other than change in lesion size are needed. Cancer 2009. © 2008 American Cancer Society.
Characterisation of virgin olive oils from European olive cultivars introduced in Tunisia
Authors: Dabbou Samia , Issaoui Manel , Servili Maurizio , Taticchi Agnese , Sifi Samira , Montedoro Gian Francesco , Hammami Mohamed 
Published: January 2009

AbstractThe behaviour of three European olive varieties, Ascolana Tenera, Koroneiki and Picholine, cultivated in the north of Tunisia, was compared to an autochthonous variety, Chétoui. Most of the quality indices and the fatty acid composition showed significant variations between the olive oils. Among the introduced varieties, the Picholine cultivar had the highest value of oleic acid (61%) whereas the Ascolana Tenera cultivar was noteworthy for its lowest content of phenolic compounds (175 mg/kg) and presented the highest level of palmitic acid. The Chétoui variety presented a high content of oleic and linoleic acids. But all samples, both the autochthonous Chétoui and the introduced cultivars, have similar levels of antioxidant compounds, with the exception of phenols. The aroma composition showed significant differences between the oils from the foreign cultivars. The major volatile component was the C‐6 aldehyde fraction whose content varied greatly between the different varieties studied: The E‐2‐hexenal content ranged from 1.6 mg/kg of oil in the Ascolana Tenera variety to >5 mg/kg for the Picholine and Koroneiki cultivars, whereas the Chétoui variety had the lowest levels of volatile compounds, with the exception of the hexanal level which was tenfold higher than in the foreign cultivars. Therefore, our results showed that two of the introduced varieties, Koroneiki and Picholine, showed good adaptation to the Tunisian cultivation conditions. So far, we claim the possibility to develop the successful cultivation of these latter imported varieties in the country.
Characterization of grape seed oil from different grape varieties (Vitis vinifera)
Authors: Pardo Jose Emilio , Fernández Enrique , Rubio Manuela , Alvarruiz Andrés , Alonso Gonzalo Luis 
Published: January 2009

AbstractIn this work, oil obtained from seeds of different red grape varieties, grown in the Autonomous Regions of Castilla‐La Mancha and Murcia (Spain), was characterized by determining physicochemical and sensory quality parameters, stability, and the composition in fatty acids and sterols. The physicochemical quality parameters (free acidity, peroxide index, K270 and wax) scored high (meaning low quality) compared with virgin olive oils, while the negative sensory attributes stood out over the positive ones. Therefore, the oil was not considered suitable for table use without undergoing a refining process. The samples showed high linoleic and low linolenic acid contents, while β‐sitosterol was the main sterol found. Drying grape seeds with hot air before extraction gave higher physicochemical quality, total phenolic content and stability, and lower wax content in comparison to air‐drying of seeds. The drying process affected the sterol composition but not the fatty acid composition.
Highly accurate photopyroelectric measurement of thermal diffusivity of vegetable oils
Authors: Dadarlat Dorin , Neamtu Camelia , Streza Mihaela , Socaciu Carmen , Bele Constantin , Dulf Francisc 
Published: January 2009

AbstractHigh‐accuracy photopyroelectric measurements, in the thermal‐wave‐resonator‐cavity configuration, were performed in order to measure the thermal diffusivity of some vegetable oils. The high resolution (relative error ±0.5%) of the above method allows for the detection of small changes in the values of this dynamic thermal parameter. The accuracy of the results is mainly due to the possibility to precisely control the variation (30‐nm step) of sample thickness, a proper selection of the range of the thickness scan (2 µm < Lm < 4 µm ˜ 5 µm), and an iterative procedure of data analysis. A correlation between thermal diffusivity and the fatty acid composition (obtained via gas chromatography) is suggested for some fresh (sunflower, hemp, flax, and soybean) oils and for hemp oil exposed to a microwave field: Thermal diffusivity appears to be determined by the overall content of polyunsaturated fatty acids.
Short‐path distillation of palm olein and characterization of products
Authors: Lin Siew Wai , Yoo Cheah Kien 
Published: January 2009

AbstractShort‐path distillation (SPD) has been a technique used to purify products containing monoacylglycerols (MAG), diacylglycerols (DAG), etc. Palm oil and its fractions contain high contents of DAG, typically 5–8%, some of which have significant effects on the crystallization behavior of the fats. A possible way of reducing the DAG to lower levels using SPD is evaluated. Distillation of refined, bleached and deodorized palm olein was performed at different temperatures (220–250 °C) and flow rates (500 and 1000 g/h). Feed oil, residue oil and distillates were characterized in terms of composition and melting and cooling behavior. The DAG content of the feed oil was 6.5%. At high evaporating temperatures, the free fatty acid (FFA) concentration in the residue oil and the distillate oil decreased for the same flow rate. Increasing the feed flow rate while maintaining constant temperature led to a greater FFA concentration in both streams. The DAG content in the distillate increased at higher temperature, reaching 68% at 250 °C, while the residue oil achieved a level of 2.8% at lower flow feeding rates. Melting and cooling behavior were influenced by the composition of DAG and triacylglycerols. Thus, the distillate oils had higher melting profiles in contrast to the feed oil and the residue oil, which had similar profiles despite the removal of higher‐melting components.