15 research outputs found
Construction of the Tricyclic Furanochroman Skeleton of Phomactin A via the Prins/Conia-Ene Cascade Cyclization Approach
No full textA substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been developed with In(OTf)(3) in CH(3)CN from 0 to 70 degrees C. These Conditions afforded very good yields of the 1-oxadecalin product in one pot and effectively suppressed the racemization of the 1-oxadecalin product with almost no enantiomeric excess (ee) loss. This cascade cyclization has been successfully employed for the construction of the highly functionalized 1-oxadecalin unit of phomactin A with an acyclic beta-keto ester and an alkynal as the substrates via a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has been readily converted to the tricyclic furanochroman skeleton of phomactin A via the epoxidation/dealkoxycarbonylation protocol under very mild conditions with 52% yield in three steps.Chemistry, OrganicSCI(E)EIPubMed20ARTICLE166534-65417
Syntheses of Diverse Natural Products via Dual-Mode Lewis Acid Induced Cascade Cyclization Reactions
No full textThe sigma/-binding properties of a series of Lewis acids was studied using DFT calculations. The results led to the identification of Zn(II)/In(III) as a suitable dual-mode Lewis acid for use in promoting cascade cyclization reactions. Based on this finding, we developed three new types of dual-mode Lewis acid induced cascade cyclization reactions and have demonstrated the utilities of each process in natural product synthesis. 1Introduction 2Dual-Mode Lewis Acids 3Prins/Conia-Ene Cascade Reaction and its Applications 4Diels-Alder/Carbocyclization Cascade Reaction and Applications 4.1First Generation Diels-Alder/Carbocyclization Cascade Reaction and its Application 4.2Second Generation Diels-Alder/Carbocyclization Cascade Reaction and its Applications 5Michael/Conia-Ene Cascade Reaction and its Applications 6ConclusionNational Natural Science Foundation of China [20972004, 21072008, 21272012, 21572006]; Science, Technology and Innovation Committee of Shenzhen [JCYJ20140509093817686, JCYJ20150626111042525]; Peking University Shenzhen Graduate SchoolSCI(E)REVIEW121394-14062
Progress towards the total synthesis of the welwitindolinone alkaloids and the discovery of a novel tandem O-H insertion Conia-ene cyclization
Get PDF2011 Spring.Includes bibliographical references.The broth of blue-green algae Hapalosiphon wewitschii and Westiella intricate was shown to possess interesting biological activity, including insecticidal and P-glycoprotein inhibiting capabilities. Upon further investigation, the welwitindolinone alkaloids were isolated from the lipophilic extracts and shown to be responsible for the observed biological activity. Herein are described efforts towards the total synthesis of the welwitindolinone alkaloids and novel chemistry developed in the process. In efforts towards N-methylwelwitindolinone C isothiocyanate, we employed a sequential O-H insertion Claisen rearrangement to provide compounds capable of undergoing a [3+2] dipolar cycloaddition to access the bicyclo[4.3.1] core. Attempts to install the requisite quaternary center of N-methylwelwitindolinone C isothiocyanate during the [3+2] dipolar cycloaddition event were unsuccessful. Ultimately, a chloronium-ion semi-Pinacol rearrangement was utilized to install the key quaternary center. Due to complications encountered during the synthesis of N-methylwelwitindolinone C isothiocyanate we shifted our focus to N-methylwelwitindolinone D isonitrile. Investigation into the construction of the bridged ether embedded within N-methylwelwitindolinone D isonitrile led to the discovery of a novel tandem O-H insertion Conia-ene cyclization
Routes to highly substituted fulvenes and applications to organometallic synthesis, 1997
Get PDFThe goal of the research presented was to develop a high yielding method for the preparation of a tetrasubstituted fulvene and to prepare a ferrocene complex incorporating a new tetrasubstituted cyclopentadienyl ligand prepared from the fulvene. By modifying the procedure of Conia, the preparation of 3,4-dimethylcyclopent-2-enone was attempted. 3 ,4-dimethylcyclopent-2-enone was treated with MeLi and [(Ph)3P=CH(Ph)2)] in order to synthesize diphenylmethylene-2,3-dimethylcyclopent-2-ene. The synthesis was not successful after several different modifications. Diphenylmethylene-2,3 -dimethylcyclopent-2-ene was to be treated with bromine, followed by triethylamine to give 3,4-dimethyl-6,6-diphenyl fulvene
Synthesis and applications of confined phosphines into hemicryptophane cages
No full textLes cages moléculaires présentent, depuis plusieurs décennies, un intérêt indéniable pour leurs nombreuses applications allant de la reconnaissance moléculaire à la catalyse supramoléculaire. Parmi cette famille de composés très vastes, les hémicryptophanes sont des molécules présentant une symétrie C3 et combinant une unité CTV (cyclotrivératrylène) liée à une autre unité de symétrie C3. En fonctionnalisant les cages avec une unité capable de complexer un métal ou aves des groupements organiques fonctionnels, il est possible d'obtenir des systèmes présentant des propriétés innovantes en organocatalyse ou catalyse métallique. Au cours de cette thèse, les travaux effectués porteront sur la synthèse de nouveaux hémicryptophanes présentant une unité phosphine endohédrale. Ces objets moléculaires pourront directement être utilisé en organocatalyse confinée de la réaction de Morita-Baylis-Hillman ou seront post-fonctionnalisés par complexation d'un atome de métal (Au(I)) pour des applications en catalyse métallique sur la réaction de Conia-ène ou encore la cycloisomérisation de 1,6-enynesMolecular cages show great interest for their many applications ranging from molecular recognition to supramolecular catalysis. Among this very large family of compounds, hemicryptophanes are molecules exhibiting C3 symmetry and combining a CTV (cyclotriveratrylene) unit linked to another C3 symmetry unit. By using a unit which can complex a metal or by functionalizing the cages with organic groups, it is possible to obtain systems with innovative properties in organocatalysis or metallic catalysis. During this thesis, the work carried out will focus on the synthesis of new hemicryptophanes with an endohedral phosphine unit. These molecular objects can be directly used in confined organocatalysis on the Morita-Baylis-Hillman reaction or will be post-functionalized by complexation of a metal atom (Au (I)) for applications in metal catalysis on the Conia-ene reaction or the cycloisomerization of 1,6-enyne
Synthesis of the 6,6,5,7-etracyclic core of daphnilongeranin B
No full textAn efficient approach toward the synthesis of the 6,6,5,7-tetracyclic core of the daphnilongeranin B, a Daphniphyllum alkaloid, is reported. The bridged 6,6-bicyclic system was constructed using a gold(I) catalysed Conia-ene reaction, while the 5-and 7-membered rings were assembled by two diastereoselective Michael addition reactions, respectively
Total Synthesis of (-)-Teucvidin
No full textA concise enantioselective synthesis of (-)-teucvidin has been achieved. Our synthetic strategy involved the diastereoselective Michael/Conia-ene cascade cyclization reaction for rapid establishment of the cis-decalin skeleton with three new stereogenic centers in one pot (72%, single diastereomer), the epozidation/dealkozycarbonylation protocol for construction of the fused furanone moiety, and the O-allylation/Claisen rearrangement protocol for construction of the all-carbon quaternary center at C9 of the clerodane skeleton.Chemistry, OrganicSCI(E)PubMed11ARTICLE112886-28891
Literary and Historical Reminiscences in the Works of Giuseppe Sabalich
No full textLo scopo di questa tesi di laurea è rintracciare gli elementi intertestuali nelle opere di Giuseppe Sabalich, il più prolifico autore zaratino a cavallo tra l’Ottocento e il Novecento. Si tratta dei monologhi: Il linguaggio senza parole, Essere... o non essere, e del proverbio in un atto Fra i due litiganti il terzo...perde. In primo monologo, Il linguaggio senza parole, il protagonista è un maestro disoccupato, che, dopo il furto della cassa scolastica, comincia a studiare i sistemi didattici e rivela la loro assurdità. Conia un’invenzione, il linguaggio senza parole, con il quale si potrebbe compiere la comprensione globale. In secondo monologo, Essere... o non essere, il protagonista si trova a fronte di un dilemma, di sposarsi o no. Qui, Sabalich critica il rapporto tra l’uomo e la donna, esaminandolo sin dai tempi passati. Questo rapporto è anche il tema del proverbio in un atto, Fra i due litiganti il terzo...perde, dove i protagonisti si trovano in un triangolo amoroso e dove una parte dovrebbe perdere. Le opere sono piene delle citazioni ed allusioni alle altre opere, ai personaggi storici e ai proverbi popolari. Un altro obiettivo di questa tesi di laurea è mostrare l’importanza del ruolo del lettore, che partecipa attivamente nella costruzione del significato del testo. Oltre al lettore, un altro fattore molto importante nella interpretazione d’un opera letteraria è la cultura, perché attraverso i codici sociali, ogni individuo costruisce il significato tramite il quale crea il suo mondo di riferimento.Cilj ovog diplomskog rada je pronaći književne i povijesne reminiscencije u djelima najplodnijeg zadarskog autora na prijelazu iz 19. u 20. stoljeće, Giuseppea Sabalicha. Djela koja se obrađuju su monolozi Il linguaggio senza parole i Essere... o non essere te poslovična jednočinka Fra i due litiganti il terzo... perde. U prvom monologu, Il linguaggio senza parole, protagonist je nezaposleni učitelj, koji, nakon što je pokrao školsku blagajnu, počinje proučavati školski sustav, otkrivajući apsurdnost istog. Promišlja o govoru bez riječi, s kojim bi se moglo ostvariti globalno razumijevanje. U sljedećem monologu, Essere... o non essere, protagonist se nalazi u dilemi - oženiti se ili ne. U ovom djelu Sabalich kritizira odnos muškarca i žene te ga preispituje. Odnos muškarca i žene također je tema i poslovične jednočinke Fra i due litiganti il terzo... perde, u kojoj se protagonisti nalaze u ljubavnom trokutu i gdje će jedna strana morati izgubiti. Sva tri djela obiluju aluzijama na druga djela, na povijesne osobe i narodne poslovice. Također je i cilj ovog diplomskog rada ukazati na važnost uloge čitatelja, koji aktivno sudjeluje u stvaranju značenja teksta. Osim čitatelja, drugi važan faktor u interpretaciji nekog književnog djela je kultura, jer kroz društvene norme pojedinac stvara značenje kojim gradi svijet oko sebe.The aim of this thesis is to trace literary and historical reminiscences in the works of the most prolific author from Zadar at the turn of the 20th century, Giuseppe Sabalich. The analyzed works are the following: two monologues Il linguaggio senza parole, Essere... o non essere, and a proverbial one-act play Fra i due litiganti il terzo... perde. In the first monologue, Il linguaggio senza parole, the protagonist is an unemployed teacher, who, after robbing the school cash register, starts to analyze the school system, unveiling its absurdity. He introduces his own innovation, a language without words, which could enable global understanding. In the next monologue, Essere... o non essere, the protagonist faces a dilemma - to marry or not. Here, Sabalich criticizes the relationship between a man and a woman and examines it since ancient times. Even in his next work, the proverbial one-act play Fra i due litiganti il terzo... perde, the author confronts the same topic, as protagonists are caught up in a love triangle and one of them will have to lose. All three works abound with quotations and allusions to other works, historical figures and proverbs. Another objective of this thesis is to point out the importance of the role of the reader, who actively participates in the construction of the meaning of the text. Apart from the reader, another important element that influences the interpretation of the literary work is culture as the reader constructs a meaning through established social norms, with which they subsequently create the world they live in
Clinical phenotype and outcomes of pneumococcal versus meningococcal purpura fulminans: a multicenter retrospective cohort study
No full textInternational audienceNo abstract availabl
Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial
No full textInternational audienceBackground: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit.Methods: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345.Findings: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69).Interpretation: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population
