Gutekunst, W.R.; Gianatassio, R.; Baran, P. S.Angew. Chem. Int. Ed. 2012, 51, 7507-7510.
Piperarborinines are simple examples of heterodimeric cyclobutane natural products isolated from pepper plants. These compounds, initially thought to have no biological activity, turned out to demonstrate a selective inhibition of cytochrome P450 2D6. These molecules presented an opportunity to develop cyclobutane C-H olefination chemistry, and in this paper, the authors demonstrate their new strategy.
"Join these comic book super heroes in a batte against organic chemistry ignorance! All varieties of superheroes are represented, from Iron Man to Captain Underpants! These superheroes will guide you through these difficult syntheses, so we hope you enjoy them!"
Shi, J.; Manolikakes, G.; Yeh, C.-H.; Guerrero, C. A.; Shenvi, R. A.; Shigehisa, H.; Baran, P. S. J. Am. Chem. Soc. 2011, 133, 8014-8027.
Cortistatin A is a steroid that is able to inhibit angiogensis without demonstrating any cytotoxicity. This is then a promising agent for treatment of not only cancer, but macular degeneration, and rheumatoid arthritis. Cortistatins are rare, so many recent synthesis approaches have been reported. Here Shi et al. report an improved synthesis of cortistatin A and related structures. Of particular importance is route through prednisone, which is abundantly available at a low price. This paper then suggests a synthesis approach through readily available starting materials, allowing for cheaper synthesis of this biologically important compound.
"Disney classics, notably: Pirates of the Caribbean, The Little Mermaid, Monsters, Inc., The Incredibles, High School Musical, Up, and Mulan, are memorable and inspirational films. These movies are not only humorous, but touch our hearts, especially High School Musical. We hope that the SSG 3 students are able to touch your heart as they use these movies to understand the reactions in this article. "
Seiple, I. B.; Su, S.; Young, I. S.; Lewis, C. A.; Yamaguchi, J.; Baran, P. S. Angew. Chem. Int. Ed. 2010, 49, 41095-1098.
Some unique facets of polycyclic dimeric pyrrole-imidazole alkaloids such as palau?amine are: nine or more nitrogen atoms, eight contiguous stereogenic centers, reactive aminal moieties, oxidation-prone pyrroles, and highly polar, non-crystalline morphologies. These unique structures have made them the focus of chemistry papers, worldwide, and have led to significant advances in synthetic methodology. Palau?amine, in particular presents an unique challenge: one of its sidechains is embedded in a hexacyclic core architecture, which contains a highly-strained trans-azabicyclo[3.3.0]octane substructure. This type of substructure is unprecedented among natural products! An alternative strategy, inspired by previous failed attempts, has led to the total synthesis of palau?amine, and is presented in this paper.
"After coming home from a nine-hour day at Double Honors Orgo II lab, you grab a can of root beer, crash on your couch, and flip on the ol? TV. But your mind are heart remain at your lab bench. The question haunts you: how are polycyclic dimeric pyrrole-imidazole alkaloids even synthesized?? Should you run back to the Chemistry Building and see if Dr. Sanford is still in her office to ask her? Fear not and just sit back ? tune in as SSG 4 and the characters of some of your favorite TV shows lead you through the total synthesis of Palau?amine. Let the marathon begin!"
Tanino, K.; Takahashi, M.; Tomata, Y.; Tokura, H.; Uehara, T.; Narabu, T.; Miyashita, M. Nature Chem. 2011, 3, 484-488.
J?rgensen, L.; McKerrall, S. J.; Kuttruff, C. A.; Ungeheuer, F.; Felding, J.; Baran, P. S. Science 2013, 341, 878-882. In 2012, the Food and Drug Administration approved the production and prescription of Picato. This drug, the first of its kind, is used from treatment of actinic keratosis, a precancerous skin condition. Its active ingredient is ingenol mebutate, an inducer of cell death; it is harvested from the sap of the plant Euphorbia peplus. Unfortunately, this sourcing process is very inefficient and expensive, only producing 1.1 mg of the compound per kilogram of plant matter. In this paper, the authors describe a simple, highly controlled, inexpensive synthesis of (+)-ingenol from (+)-3-carene. The results represent a viable strategy for efficient chemical production and commercial synthesis. This work was initiated through a partnership with LEO Pharma, the developer of Picato.
"Most people would consider fast food restaurants and health to be on opposite sides of the battle. Well, now the fast food joints of SSG 2 have teamed up to synthesis (+)-ingenol, a chemical with anti-cancerous properties. Join the students of our class in cookin? something up! "
Su, S.; Rodriguez, R. A.; Baran, P. S. J. Am. Chem. Soc. 2011, 133, 13922-13925.
The bioactive pyrrole-imidazole marine alkaloid (PIA) family of molecules contains axinellamines A and B, massadine, massadine chloride, and palau?amine, all of which have a common chemical progenitor. The prior synthesis of this progenitor was inefficient, but was largely refined by the group to allow for scalable syntheses of the PIA family, namely axinellamines A and B. By means of their research, three methodological advances were also made, involving an ethylene glycol-assisted Pauson-Khand cycloaddition reaction to minimize decomposition, a chemoselective In/Zn-mediated Barbier-type reaction to allow for effective desymmetrization, and a stereocontrolled TfNH2-assisted chlorination-spirocyclization reaction.
"These chemical discoveries are astounding, but were they actually made by aliens? Was the laboratory located in a high-security research facility in the middle of the desert? Are there connections with these reactions and a secret society?s plot to take over the world? Who knows!? ? Grab your shoddy video recorder and Nana?s old Polaroid camera and join SSG 5 as we delve into the realm of conspiracy theories!"
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