Progress Towards the Total Synthesis of Amphidinolide C

A second generation catalyst for the Mukaiyama oxidative cyclization for the formation of trans-THF rings is described. Co(nmp)2, displays increased stability to the reaction conditions, resulting in lower catalyst loadings, lower reaction temperatures, and significantly higher purity and yields of the products. Three procedures have been developed with this new water-soluble catalyst that greatly simplifies the post-reaction purification, making this procedure the premier method of forming trans-THF rings. This new catalyst has been applied towards the total synthesis of the potently bioactive macrocycle, Amphidinolide C. Herein we report the successful synthesis of several fragments of the natural product, and our attempts at coupling them to complete the synthesis. The C(1)-C(9) was achieved via two routes, both utilizing the highly effective oxidation catalyst Co(nmp)2 to form the methyl substituted trans-THF ring. Synthetic highlights include a regioselective Shi epoxidation, and the design and introduction of a novel Lewis acid (BF2OBn×OEt2) to facilitate a stereoselective reductive epoxide opening. The C(18)-C(34) fragment was also achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. Synthetic highlights of this fragment include a selective methylation of a diyne, and a highly selective alkynylation of a THF aldehyde, achieving excellent dr (\u3e20:1) without the addition of an external chiral compound. Advanced intermediates comprising the entirety of the carbon backbone of the molecule have been synthesized, which in theory could complete the total synthesis in as few as two bond forming steps

Analysis of errors in verbal fluency tasks in patients with chronic schizophrenia

Background and Objectives: Even if verbal fluency deficits have been described in Schizophrenia, error pattern in this test has not been analyzed in detail in the literature. The pattern analysis of such errors could contribute to the understanding of the factors that influence poor task performance in schizophrenia. In this study we analyzed the intrusion and perseveration errors in verbal fluency tasks in patients with chronic schizophrenia. Methods: 87 patients diagnosed with Chronic Schizophrenia and 87 healthy controls were included in this investigation and were assessed with four Phonological and Semantic Verbal Fluency tasks. Results The results of this study showed that at least half of schizophrenic patients produced perseverative errors on verbal fluency and about made intrusion errors. The severity of negative symptoms, the severity of Formal Thought Disorder and pharmacological variables were significant moderators to errors in Verbal Fluency performance. Conclusions Errors in Verbal Fluency can be explained by the interaction of different variables in patients with schizophrenia. Schizophrenia is a psychological pathology with great phenomenological complexity and its particularities can only be explained by the consideration of the multiple factors involved in its manifestation.Fil: Galaverna, Flavia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Bueno, Adrián Marcelo. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Morra, Carlos A.. Prof. León S. Morra Sanitarium; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roca, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Torralva, Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

BF2OBn∙OEt2: A Novel Lewis Acid and its use in a Regio- and Stereo-selective Opening of Trisubstituted Epoxides and its Application Towards Amphidinolide C

The generation of a new Lewis acid (BF2OBn·OEt2) has been reported, and its usefulness has been demonstrated in the regio- and stereoselective ring-opening of trisubstituted epoxides. This Lewis acid is one in a series of new Lewis acids generated from BF3·OEt2 that display varying levels of Lewis acidity. When paired with a modified Shi epoxidation protocol, highly functionalized propionate units, such as those found in a wide variety of natural products, can be accessed. In conjunction with a Mukaiyama oxidative cyclization employing our second generation catalyst Co(nmp)2, this procedure ultimately culminated in the shortest and highest yielding route towards the methyl-substituted trans-tetrahydrofuran (trans-THF) fragment present in amphidinolide C, C2, and F

Natural zeolites and white wines from Campania region (Southern Italy): a new contribution for solving some oenological problems

The purpose of this research is to provide a new mixture of Campanian zeolitized tuffs for solving two specific problems in the production of white wines: the protein and tartaric stability. In fact, a very frequent cause of turbidity and formation of organic deposits in white wines is the occurrence of thermolabile and thermostable proteins colloidal suspensions which precipitate in time, especially in summertime and during the storage and transport. Normally, to mitigate this risk wine producers use organic and inorganic stabilizers and clarifiers. The best known treatment, recognized also by the International Organisation of Vine and Wine (OIV) foresees the use of bentonite with a montmorillonite content not lower than 80%. The present paper aims at evaluating the use of two high zeolite grade Italian volcanoclastites such as the Neapolitan Yellow Tuff (NYT) and the Yellow Facies of the Campanian Ignimbrite (YFCI), in the treatment of three peculiar white wines of the Campanian region (Southern Italy): Falanghina, Fiano di Avellino and Greco di Tufo. Granulates were produced starting from tuff blocks as provided by quarries. Some grain size fractions have been prepared to investigate the zeolite content (phillipsite + chabazite + analcime) by X-ray diffraction (XRD). A 2-5 mm grain size fraction was chosen for NYT and a 5-10 mm for YFCI. Three Campanian monocultivar white wines were used for the test: the Falanghina 2006 vintage, the Fiano di Avellino DOCG 2007 vintage, and the Greco di Tufo DOCG 2008 vintage. 48 samples with mixture of the zeolitized tuffs, 1 sample with mixture of a synthetic zeolite A and 1 sample with mixture of a commercial sodium activated bentonite were prepared. ICP-OES analysis for the determination of ECEC, Ion Chromatography (IC) analyses for the determination of some major cations and Turbidimetric tests for the definition of the protein stabilization process before and after treatments were also carried out. It was evidenced that high zeolitized tuff/wine ratios enable the protein stabilization whereas a significant decrease of potassium ion after the treatment with a zeolite-rich powder improves the tartaric stability, a serious problem in all the wine productions. The results of these tests refer to a laboratory scale research. A transfer of the experiment to a pilot plant scale is in progress

Gram scale synthesis of the C(18)-C(34) fragment of amphidinolide C.

The synthesis of the C(18)-C(34) fragment of amphidinolide C has been achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. The highly convergent approach will facilitate the synthesis of analogues, including the C(18)-C(29) fragment of amphidinolide F. Synthetic highlights include the selective methylation of a diyne, and the highly efficient use of a second generation cobalt catalyst in the Mukaiyama oxidative cyclization to form the trans-THF ring

Gram scale synthesis of the C(1)-C(9) fragment of amphidinolide C

An allylic cis-epoxide prepared by Sharpless asymmetric epoxidation was transformed in 9 steps and 41% overall yield to the cyclization precursor 4 via a key one carbon homologation. Cobalt catalyzed aerobic oxidative cyclization of 4 gave the trans-THF in 94% yield at gram scale. Subsequent manipulations, including a Still-Gennari olefination, Sharpless asymmetric dihydroxylation, Corey-Fuchs alkynylation and Kazmaier hydrostannylation provided the fully functionalized C(1)-C(9) fragment 2 suitable for cross coupling. The sequence is readily scalable and provides gram quantities of

Ascent of Bubbles in Magma Conduits Using Boundary Elements and Particles

AbstractWe investigate the use of the Multipole-accelerated Boundary Element Method (BEM) and of the Singularity Method for studying the interaction of many bubbles rising in a volcanic conduit. Observation shows that the expression of volcanic eruption is extremely variable, from slow release of magma to catastrophic explosive manifestation. We investigate the application of the Fast Multipole Method to the solution of (i) the Boundary Element Formulation of the Stokes flow and of (ii) the particle formulation using the Stokeslets, the Green Function of the Stokes flow law, as a particle kernel. We show how these implementations allow for the first time to numerically model in a dynamic setting a very large number of bubbles, i.e few thousands with the BEM models, allowing investigating the feedback between the single bubble deformation and their collective evolution, and few hundred of thousands of bubbles with the particle approach. We illustrate how this method can be used to investigate the intense interaction of a large number of bubbles and suggest a framework for studying the feedback between many bubbles and a complex thermal nonlinear magmati