Dimer Interface Destabilization of Photodissociative Dronpa Driven by Asymmetric Monomer Dynamics.

Photoswitchable Dronpa (psDronpa) is a unique member of the fluorescent protein family that can undergo reversible photoinduced switching between fluorescent and dark states and has recently been engineered into a dimer (pdDronpaV) that can dissociate and reassociate as part of its photoswitchable pathway. However, the specific details of the protein structure-function relationship of the dimer interface along with how the dimer proteins interact with each other upon chromophore isomerization are not yet clear. Classical molecular dynamics simulations were performed on psDronpa as monomers and dimers as well as the pdDronpaV dimer and with / chromophore structures.

Investigation of the Organocatalytic Chlorination of 2-Phenylpropanal.

Results of an examination of the organocatalytic enantioselective α-chlorination of 2-phenylpropanal are described. Synthetic investigation including the screening of primary and secondary aminocatalysts, many different reaction conditions, and other α-branched aldehydes show that especially primary aminocatalysts can catalyze the formation of the α-chloro branched aldehydes in good yields, but only with moderate enantioselectivities. In order to try to understand the challenge in obtaining high enantioselectivity for the aminocatalytic α-chlorination of α-branched aldehydes a series of experimental investigations were performed employing 2-phenylpropanal as a model system.

Enantioselective 1,3-Dipolar [6+4] Cycloaddition of Pyrylium Ions and Fulvenes towards Cyclooctanoids.

Organocatalytic enantioselective 1,3-dipolar [6+4] cycloadditions of pyrylium ion intermediates with fulvenes promoted by a chiral primary amine catalyst have been developed to proceed in moderate to good yields and high enantioselectivities. The resultant chiral bicyclo[6.3.

Predicting Rearrangement-Competent Terpenoid Oxidation Levels.

Results of density functional theory calculations on rearrangements of potential biosynthetic precursors to the sesquiterpenoid illisimonin A reveal that only some possible precursors, those with certain specific oxidation patterns, are rearrangement-competent.

Secondary Carbocations in the Biosynthesis of Pupukeanane Sesquiterpenes.

The results of quantum chemical calculations on putative biosynthetic carbocation cyclization/rearrangements leading to pupukeanane and related sesquiterpenes indicate that a secondary carbocation proposed as an intermediate is not a minimum on the potential energy surface and instead resides in a region of the potential energy surface associated with a plateau containing multiple exit channels.

Synthesis of Highly Stereodefined Tetrasubstituted Acyclic All-Carbon Olefins via a Syn-Elimination Approach.

An efficient synthesis of stereodefined tetrasubstituted acyclic all-carbon olefins has been developed via a bis(2,6-xylyl)phosphate formation of stereoenriched tertiary alcohols, followed by in situ syn-elimination of the corresponding phosphates under mild conditions. This chemistry tolerates a wide variety of electronically and sterically diverse substrates and generates the desired tetrasubstituted olefins in high yields and stereoselectivities (>95:5) in most cases. This stereocontrolled olefin synthesis has been applied to the synthesis of anticancer drug tamoxifen in three steps from commercially available 1,2-diphenylbutan-1-one in 97:3 stereoselectivity and 78% overall yield.

Biomimetic Platinum-Promoted Polyene Polycyclizations: Influence of Alkene Substitution and Pre-cyclization Conformations.

Results of kinetic experiments and quantum chemical computations on a series of platinum-promoted polycyclization reactions are described. Analyses of these results reveal a reactivity model that reaches beyond the energetics of the cascade itself, incorporating an ensemble of pre-cyclization conformations of the platinum-alkene reactant complex, only a subset of which are productive for bi- (or larger) cyclization and lead to products. Similarities and differences between this scenario, including reaction coordinates for polycyclization, for platinum- and enzyme-promoted polycyclization reactions are highlighted.