Enantioselective Total Synthesis of (—)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine

The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (−)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (−)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family

Sur les montagnes de Zu

Réussirons-nous à surmonterorgueil et jalousiesur les montagnes de Zu ?Tsui Hark Pour des milliers d'années la Force du Bien et la Force du Mal ne vivront jamais en paix. Aube (Cecilia Cheung), qui dirige la secte Kun Lun, tombe amoureuse de son disciple Roi-Ciel (Ekin Cheng). Mais Insomnia, chef de la Force du Mal, attaque Kun Lun et détruit Zaube et la secte tout entière. Deux cents ans plus tard, la Force du Mal est de nouveau à l'attaque. Roi-Ciel jure de détruire Insomnia, mais rencontre..

The Development of a Synthetic Strategy Toward Dihydrooxepine-Containing Epipolythiodiketopiperazines: Enantioselective Total Synthesis of (-)-Acetylaranotin and Related Investigations

To the chemist, the epipolythiodiketopiperazine (ETP) fungal metabolites represent a fascinating family of natural products, not only for their unique structural elements, but also for the unusual modes by which they are hypothesized to exert their biological activities. Though efforts at the total synthesis of these molecules have led to an evolution of innovative synthetic methodologies and strategies, challenges remain—particularly with respect to acid-sensitive and highly oxygenated ETP structures, such as those containing one or more dihydrooxepine ring. As part of a broad research program targeting ETP natural products, we have developed a synthetic strategy towards dihydrooxepine-containing ETPs. Herein, the enantioselective total synthesis of (–)-acetylaranotin is described. This represents the first total synthesis of any dihydrooxepine-containing ETP natural product. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. Our strategy was extended to the synthesis of a small panel of epitetrathiodiketopiperazines, including the natural products SCH64877 and emethallicin C as well as analogs, which are currently being evaluated for biological activity. Furthermore, preliminary investigations into the synthesis of dihydrooxepine-containing macrocycles have been conducted, with a particular focus on the preparation of bis(ortho-methoxyaryl) ethers. Finally, as part of our efforts to further explore interesting side reactions observed during synthetic studies toward acetylaranotin, a catalytic asymmetric double (1,3)-dipolar cycloaddition reaction was developed. This reaction provides access to highly substituted, enantioenriched pyrrolidizines from inexpensive, commercially available starting materials. Furthermore, the reactivity of diketopiperazine intermediates prepared en route to acetylaranotin toward aerobic oxidation was briefly explored.</p

Catalytic asymmetric synthesis of highly substituted pyrrolizidines

A catalytic asymmetric double (1,3)-dipolar cycloaddition reaction has been developed. Using a chiral silver catalyst, enantioenriched pyrrolizidines can be prepared in one flask from inexpensive, commercially available starting materials. The pyrrolizidine products contain a variety of substitution patterns and as many as six stereogenic centers

Hasta que llegó Leone

Aguilar, C.; Codelli, L. (2002). Hasta que llegó Leone. Nosferatu. Revista de cine. (41):22-31. http://hdl.handle.net/10251/41294.Importación Masiva22314

Crosslinking Studies of Protein-Protein Interactions in Nonribosomal Peptide Biosynthesis

SummarySelective protein-protein interactions between nonribosomal peptide synthetase (NRPS) proteins, governed by communication-mediating (COM) domains, are responsible for proper translocation of biosynthetic intermediates to produce the natural product. In this study, we developed a crosslinking assay, utilizing bioorthogonal probes compatible with carrier protein modification, for probing the protein interactions between COM domains of NRPS enzymes. Employing the Huisgen 1,3-dipolar cycloaddition of azides and alkynes, we examined crosslinking of cognate NRPS modules within the tyrocidine pathway and demonstrated the sensitivity of our panel of crosslinking probes toward the selective protein interactions of compatible COM domains. These studies indicate that copper-free crosslinking substrates uniquely offer a diagnostic probe for protein-protein interactions. Likewise, these crosslinking probes serve as ideal chemical tools for structural studies between NRPS modules where functional assays are lacking

Il Cinema Ritrovato 31e édition (Bologne 24 juin – 2 juillet 2017)

Il Cinema Ritrovato est frappé de boulimie, conséquence inévitable pour une manifestation devenue le rendez-vous annuel des conservateurs de cinémathèques, des restaurateurs de films, des historiens du cinéma, et d’innombrables cinéphiles. Huit jours de projections dans cinq salles sans compter les projections du soir dans deux lieux en plein air, notamment la mythique Piazza Maggiore au pied de San Petronio ; enfin des conférences, des rencontres, des master class dans la salle Cervi et dans..

Enantioselective Synthesis of (−)-Acetylapoaranotin

The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (−)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipolar cycloaddition reactions. The formal syntheses of (−)-emethallicin E and (−)-haemotocin are also achieved through the preparation of a symmetric cyclohexadienol-containing diketopiperazine

« Il Cinema ritrovato »

Inutile d’insister une nouvelle fois sur la richesse de la programmation bolognaise. Il Cinema ritrovato, année après année, prouve la dimension patrimoniale du cinéma comme référence culturelle majeure de l’histoire du xxe siècle. Pour sa 28e édition, la manifestation s’est encore enrichie, dédoublant ses projections nocturnes et alimentant en continu quatre salles. Et pour ajouter encore à une offre pléthorique, Il Cinema ritrovato était précédé cette année par un colloque « 100 anni di Cha..