The ﬁ rst totalsynthesis of 5-(1-hydroxy-1-ethyl)-2-isopropyliden-2H-benzofuran-3-one, is reported in its racemic and in one of its optically active [(S)-( )] forms. This heterocycle, isolated from Verbesina luetzelburgii, is the only known 2-isopropyliden-2H-benzofuran-3-one produced by species of Verbesina. The sequence took place in eight steps and 19% overall yield (up to 33% for the chiral form), from 4 0 -hydroxyacetophenone. It entailed carbonyl group protection as the 1,3-dioxolane and a phenol ortho formylation, followed by a Williamson etheri ﬁ cation with chloroacetone and an organocatalytic cross-aldolization, to a ﬀ ord a 2-acetyl-2,3-dihydrobenzofuran-3-ol intermediate. The latter underwent a methyl Grignard addition to the carbonyl moiety, followed by selective oxidation of the benzylic alcohol and deprotection, resulting in a b -hydroxy diketone derivative. A MsCl-assisted dehydration of the tertiary alcohol, established the isopropylidene motif, whereas the syntheses culminated by chemical or enzymatic (carrot, celeriac) selective reductions of the exocyclic carbonyl group.
2) The asymmetric Robinson annulation / intramolecular aza-Michael reaction leading to decahydroquinolines in a single step, from an achiral and acyclic simple E-keto ester, is not feasible using the classical reaction conditions developed by Jørgensen to synthesize cyclohexenones. After the initial organocatalyzed Michael addition, treatment with acid to promote the dealkoxycarbonylation and intramolecular aldol reaction failed, probably due to the presence of the nucleophilic nitrogen atom in the structure. In contrast, if LiOH is added after the organocatalysis step, the Robinson annulation and the following azacyclization take place in very good yield. The method has been optimized after screenings for the solvent, temperature, additives and catalysts. The resulting decahydroquinoline building block has been used in the totalsynthesis of the phlegmarine alkaloid lycoposerramine Z, which has been efficiently synthesized: 10 steps and 20% overall yield (see Scheme 5.2).
The present work is on the totalsynthesis of the natural compounds and/or analogues of Bengamides, Gummiferol and Depudecin. The target molecules, selected in virtue of their prominent biological activity as antibiotic and antitumor agents are featured by the presence of one or two epoxide groups and were synthesized by application of a novel methodology of asymmetric epoxidation based on the use of a new class of chiral sulfur ylides. The synthetic routes described in this thesis employed cheap and readily available starting materials and all the targeted molecules were reached in a moderate to good overall yield, except for the case of Depudecin, whose final step has not yet been accomplished.
Variolin B is a member of a family of marine alkaloids isolated from an extremely rare Antarctic sponge, Kirkpat- rickia varialosa. 1 The potent antitumoral activity found for variolin B and some analogs and the fact that the natural compound is no longer available from its natural source have led to several groups to develop the total syntheses of the natural alkaloid. 1,2 From the three reported total syntheses, those of Molina 3 and Alvarez 4 used a similar strategy to build up the tricyclic heterocyclic core, with the pyrimidine ring being constructed by an annelation method on the 7-azaindole system. In the strategy described by Morris 5 the tricyclic system is formed from pre-existent pyridine and pyrimidine rings using the possi- bilities oﬀered by a highly symmetrical key intermediate.
18 (a) S. Bhandari and S. Ray, Synth. Commun., 1998, 28, 765– 771; (b) G. Bartoli, M. Bosco, A. Carlone, R. Dalpozzo, E. Marcantoni, P. Melchiorre and L. Sambri, Synthesis, 2007, 3489–3496; (c) J. S. Carey, D. Laﬀan, C. Thomson and M. T. Williams, Org. Biomol. Chem., 2006, 4, 2337–2347; (d) K. Alfonsi, J. Colberg, P. J. Dunn, T. Fevig, S. Jennings, T. A. Johnson, H. P. Kleine, C. Knight, M. A. Nagy, D. A. Perry and M. Stefaniak, Green Chem., 2008, 10, 31–36; (e) H. Ueki, T. K. Ellis, M. A. Khan and V. A. Soloshonok, Tetrahedron, 2003, 59, 7301–7306; (f) R. J. Ternansky, C. L. Jordan, J. A. Eudaly and J. S. Kasher, J. Med. Chem., 1993, 36, 2332–2334.
Theodorakis and co-workers developed an elegant metal-catalyzed strategy towards the synthesis of common guaiane-type tricylic skeleton. However, this approach suffers from major limitations with a low diastereoisomeric ratio (3:1 d.r.) in the cycloaddition reaction and a total number of 28 steps from commercially available (R)-pantolactone to access to (-)-englerin A II-1 (less than 1% overall yield). Indeed the guaiane-type tricylic sesquiterpene skeleton II-48 was readily obtained in 12 steps and 6% overall yield (80% per step in average), but access to the final product required a further 15 steps including oxidation/reduction reactions and inversion of stereocenters.
These preliminary results were not encouraging. The C-Si bond revealed to be very robust, as it remained intact upon treatment with two different fluoride sources (Table 25, entries 1 and 2). Additionally, most of the reactions attempted to achieve the nucleophilic attack of the allylsilane 29d on an aldehyde resulted in the decomposition of the allylsilane (Table 25, entries 3-8). Oxidation of the C-Si bond (Table 25, entry 9) or the Hiyama- coupling (Table 25, entry 10) also failed to give the desired products. In order to test the ability of the newly isolated digold(I) hydride I, we developed preparative synthesis of this air-stable complex that led to a 70% isolated yield (Scheme 61, [eq. 1]). This complex was then subjected to the optimized reaction conditions and afforded allylsilane 29d in a surprising 21% yield (Scheme 61, [eq. 2]). To the best of our knowledge, this is the first time that a gold(I) hydride complex was shown to be a competent catalyst with turnover, as all previously reported complexes have been used in stoichiometric quantities. 128
The human kidneys are responsible for continually cleansing blood of metabolic waste products (such as urea, uric acid, creatinine), excess ions, and excess water. The resultant filtrate is then transported to the ureter to be removed as urine. Approximately 20% of the blood supply is routed to the kidneys at any time in order to provide a continual means of removing potentially toxic materials from the blood. The water removal from the kidneys serves as a secondary means of controlling blood pressure, as total blood volume is a factor in venous return, cardiac output, and thus arterial pressure. There are two kidneys, each consisting of a network of millions of individual mass transfer elements called nephrons. Transport occurs across the surface of the nephron. As is the case with the lungs, which have similar elements called alveoli, the nephrons provide a means of greatly expanding the surface area available for mass transfer within a constrained volume. The theory is similar to that of a single large sphere as compared to millions of smaller spheres within the same volume. The net surface area of the large sphere is much smaller than that of the combined surface area of the numerous small spheres. Thus, mass transfer of metabolic waste products occurs by branching blood into smaller and smaller channels until the actual mass transfer occurs at the small end point—the nephron. Again, this is similar to the trachea branching into the bronchi and eventually to the alveoli in the lungs.
Implementación mantención y viajes culturales JJVV Alto Barrancas (población 30 de marzo) + reparación de techo y pintado de sede social JJVV Sor Teresa + mobiliario urbano JJVV Nueva Esperanza + implementación sede Agrupación San Antonio de Padua + compra de materiales para talleres y actividades recreativas. Total de votos: 896
Os antecedentes de Nimbos remóntanse, fundamentalmente, á revista Alba, que comezou a súa andaina na Coruña para pasar de contado a Vigo. Desta publi- cación saíron, entre 1948 e 1956, un total de dezaseis números. Xosé María Díaz Castro chega a Alba nos 50, da man de Aquilino Iglesia Alvariño, o seu grande amigo e guieiro poético no Seminario de Mondoñedo. Aquilino fora tamén quen o levara, en 1940, ao colexio León XIII de Vilagarcía de Arousa, do que o de Sei- vane era director, centro no que Xosé María permaneceu como profesor ata 1947. Díaz Castro aparece nas páxinas da revista dirixida por Ramón González-Alegre como poeta en galego e castelán e, así mesmo, como tradutor de Chesterton e de Rilke. As poesías de Alba en galego son seis, das que recuperará catro para Nimbos (“Penélope” e “Terra sucada”  e mais “A cerna” e “Cortina” ), que pasou ao libro con modificacións. Porén, no decenio anterior, publicara outros dous poemas que tamén integrará en Nimbos: “Con este alento” (1947), no vespertino compostelán La Noche, retitulada “Coma brasas”, e “Terra e mar” (1946), na revis- ta viguesa Cartel de Julio Sigüenza, á que pon novo título, “ Ai, capitán”, e somete a importantes cambios.
una brazada. Nunca más. Sin embargo, este cambio no llega de for- ma natural. A pesar de que Total Immersion no le proporciona se- siones de entrenamiento, le garantiza que tiene trabajo de sobra. Co- mo ya hemos mencionado anteriormente, las técnicas que necesita para mejorar significativamente su forma de nado –equilibrio diná- mico, nado en el cuadrante frontal, nadar sobre el costado– no son naturales, ni instintivas. Deberá tomar una decisión consciente pa- ra nadar de esta forma, e incluso, cuando ya lo haya conseguido, aun notará sensaciones ajenas, órdenes extrañas que recorren el sistema nervioso central, movimientos que, al principio, le resultarán pecu- liares. Su desafío es cambiar esto para que estos movimientos se con- viertan en automáticos. Esto significa que si desea ir más allá de la simple comprensión de cómo nadar con la máxima eficacia, si, a par- tir de ahora, quiere nadar siempre de esa forma y convertirla en una costumbre, deberá practicar modificaciones específicas para la bra- zada y continuar practicándolas constantemente. Piense que se tra- ta de una nueva forma de entrenar, un entrenamiento dirigido al sis- tema nervioso en lugar de al sistema aeróbico.