Investigations into the effectiveness of deuterium as a "protecting group" for C-H bonds in radical reactions involving hydrogen atom transfer.

addresses: School of Biosciences (originally Department of Chemistry), University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD, UK. [email protected]: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2008 Royal Society of ChemistryCompetition experiments have been carried out to determine the extent to which deuterium can be used as a protecting group for carbon-hydrogen bonds in radical-based intramolecular hydrogen atom transfer processes

Highly diastereoselective synthesis of substituted pyrrolidines using a sequence of azomethine ylide cycloaddition and nucleophilic cyclization

Abstract: Although cycloadditions of azomethine ylides usually give mixtures of endo/exo adducts, we successfully tuned the mechanistic path of a new reaction cascade to afford substituted pyrrolidines in high yields and diastereomeric purity. This was achieved by forcing the demetalation of tin- or silicon-substituted iminium ions, followed by azomethine ylide cycloaddition and nucleophilic cyclization. Structural complexity is thus built rapidly in a fully controlled one-pot reaction cascade

Biogenetically-Inspired Total Synthesis of Epidithiodiketopiperazines and Related Alkaloids

Natural products chemistry has historically been the prime arena for the discovery of new chemical transformations and the fountain of insights into key biological processes. It remains a fervent incubator of progress in the fields of chemistry and biology and an exchange mediating the flow of ideas between these allied fields of science. It is with this ethos that our group has taken an interest in and pursued the synthesis of a complex family of natural products termed the dimeric epipolythiodiketopiperazine (ETP) alkaloids. We present here an Account of the highly complex target molecules to which we pegged our ambitions, our systematic and relentless efforts toward those goals, the chemistry we developed in their pursuit, and the insight we have gained for their translational potential as potent anticancer molecules.National Institute of General Medical Sciences (U.S.) (Grant GM089732)Amgen Inc

Gold(I)-Catalyzed Coupling Reactions for the Synthesis of Diverse Small Molecules Using the Build/Couple/Pair Strategy

The build/couple/pair strategy has yielded small molecules with stereochemical and skeletal diversity by using short reaction sequences. Subsequent screening has shown that these compounds can achieve biological tasks considered challenging if not impossible (‘undruggable’) for small molecules. We have developed gold(I)-catalyzed cascade reactions of easily prepared propargyl propiolates as a means to achieve effective intermolecular coupling reactions for this strategy. Sequential alkyne activation of propargyl propiolates by a cationic gold(I) catalyst yields an oxocarbenium ion that we previously showed is trapped by C-based nucleophiles at an extrannular site to yield α-pyrones. Here, we report O-based nucleophiles react by ring opening to afford a novel polyfunctional product. In addition, by coupling suitable building blocks, we subsequently performed intramolecular pairing reactions that yield diverse and complex skeletons. These pairing reactions include one based on a novel aza-Wittig-6π-electrocyclization sequence and others based on ring-closing metathesis reactions.Chemistry and Chemical Biolog