02 junio 2007

Crambescidin 800 . Accelerating the discovery of biologically active small molecules using a high-throughput yeast halo assay.

Gassner NC, Tamble CM, Bock JE, Cotton N, White KN, Tenney K, St Onge RP, Proctor MJ, Giaever G, Nislow C, Davis RW, Crews P, Holman TR, Lokey RS.
J Nat Prod. 2007 Mar;70(3):383-90. Epub 2007 Feb 10.
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
The budding yeast Saccharomyces cerevisiae, a powerful model system for the study of basic eukaryotic cell biology, has been used increasingly as a screening tool for the identification of bioactive small molecules. We have developed a novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The new screen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides a concentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testing materials including 3104 compounds from the NCI libraries, 167 marine sponge crude extracts, and 149 crude marine-derived fungal extracts. There were 46 active compounds among the NCI set. One very active extract was selected for bioactivity-guided fractionation, resulting in the identification of crambescidin 800 as a potent antifungal agent.

Synthesis of Pyrrolo-isoquinolines Related to the Lamellarins Using Silver-Catalyzed Cycloisomerization/Dipolar Cycloaddition.

Su S, Porco JA Jr.
J Am Chem Soc. 2007 Jun 1 .
Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, Boston, Massachusetts 02215.

Synthesis of pyrrolo-isoquinolines related to the lamellarin alkaloids employing silver-catalyzed cycloisomerization-dipolar cycloaddition of alkynyl N-benzylidene glycinates is described. Mechanistic studies revealed Ag(I)-catalyzed cycloisomerization to an azomethine ylide as a key step for formation of angular pyrrolo-isoquinolines.Date of Electronic Publication: 2007 Jun 1