Total Synthesis of Kopsinitarine E.

Kopsinitarines A-E are complex octacyclic caged Kopsia alkaloids with strained cage skeletons and a unique cyclic hemiaminal bridge that makes total synthesis challenging. Herein, we disclose the first total synthesis of kopsinitarine E. The key synthetic features include a SmI -mediated radical cascade cyclization and a subsequent semi-pinacol rearrangement to install the key carbocyclic skeleton, a chemoselective hydrosilyl amide reduction to construct the hemiaminal ether bridge, and an intramolecular Mannich reaction to establish the highly strained cage system.

Oxidative coupling strategies for the synthesis of indole alkaloids.

Direct bond formation between two C-H bonds is most challenging but imperative for efficient organic synthesis. Recently, significant progress has been made in direct functionalization of indole through oxidative coupling reactions with other nucleophiles such as enolates and phenols. Both intermolecular and intramolecular coupling reactions can be conducted under the action of base/oxidants or oxidants alone.

Expanding Diversity without Protecting Groups: (+)-Sclareolide to Indolosesquiterpene Alkaloid Mycoleptodiscin A and Analogues.

Short and scalable synthesis of the complex pentacyclic indolosesquiterpene natural product mycoleptodiscin A has been achieved from commercially available diterpenoid (+)-sclareolide in 19% overall yield. This approach allows one to prepare various analogues of mycoleptodiscin using McMurry cyclization as a key reaction with just three chromatographic purifications.

Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified FGFR1 in lung cancer.

Unlabelled: The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other recurrent amplifications, the 8p12 region included multiple centers of amplification, suggesting marked genomic heterogeneity.