The Total Synthesis of (–)-Scabrolide A

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone–olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and complete the total synthesis

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones

The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF_3)_3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee’s up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee

The Total Synthesis of (–)-Scabrolide A

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone–olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and complete the total synthesis

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014

Enantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme

An enantioselective total synthesis of the norditerpenoid alkaloid nigelladine A is described. Strategically, the synthesis relies on a late-stage C–H oxidation of an advanced intermediate. While traditional chemical methods failed to deliver the desired outcome, an engineered cytochrome P450 enzyme was employed to effect a chemo- and regioselective allylic C–H oxidation in the presence of four oxidizable positions. The enzyme variant was readily identified from a focused library of three enzymes, allowing for completion of the synthesis without the need for extensive screening

Nucleophilic Catalysis of <i>MeON</i>-Neoglycoside Formation by Aniline Derivatives

Neoglycosylations are increasingly being employed in the synthesis of natural products, drug candidates, glycopeptide mimics, oligosaccharide analogues, and other applications, but the efficiency of these reactions is usually limited by slow reaction times. Here, we show that aniline derivatives such as 2-amino-5-methoxybenzoic acid enhance the rate of acid-catalyzed neoglycosylation for a range of sugar substrates up to a factor of 32 relative to the uncatalyzed reaction

Differential drivers of chemical defenses in three widespread pine species along a 1500-m elevational gradient: a test of the elevational gradient in plant defense hypothesis

1. The elevational gradient in plant defense (EGPD) hypothesis posits that natural enemy pressures increase positively alongside temperature across elevational climatic gradients, thereby selecting for enhanced defenses at lower elevations while leaving plants less defended at higher elevations. Phylogenetically constrained tests of this hypothesis in tree populations are exceedingly rare. Nevertheless, the presumed presence of poorly-defended trees has been invoked as an important driver of recent pest outbreaks at higher elevations than historically common. 2. Tree age, growth rate, and size have all been correlated with levels of tree defenses. Thus, we sought to disentangle the interacting influences of these properties from possible elevational climatic effects on monoterpene composition, concentrations, and diversity of constitutive resin within three widespread pines (Pinus contorta, Pinus ponderosa, and Pinus flexilis) across a 1532 m elevational transect in the Rocky Mountains, Colorado, USA. 3. Collectively, elevation and tree properties were relatively weak predictors of defenses in P. ponderosa and P. flexilis, but explained ~ 75% of variation in monoterpene concentration and ~ 50% of diversity in P. contorta. 4. Increasing tree age had the greatest positive influence on monoterpene concentration and diversity in P. contorta, while increasing tree size had a negative influence suggesting a potential lifelong tradeoff between tree growth and defense. Elevation had a significant, negative influence on monoterpene concentration but little to no effect on monoterpene diversity in P. contorta. 5. Overall, we found some support for the EGPD hypothesis within P. contorta, but no support within P. ponderosa or P. flexilis. Our results suggest the presence of divergent conifer defense allocation strategies and drivers even among congeners growing in shared environments. An improved understanding of the controls on tree defenses, particularly possible influences of climate-based drivers, is necessary for predicting forest pest dynamics under global change scenarios.</jats:p

The Total Synthesis of (–)-Scabrolide a

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone-olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and to complete the total synthesis.</jats:p