14 research outputs found
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
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
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
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
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
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