The mechanism and stereoselectivity in an organocatalyzed triple cascade reaction between an aldehyde, electron deficient olefin and an alpha,beta-unsaturated aldehyde are investigated for the first time using density functional theory. The factors responsible for high levels of observed stereoselectivity (Enders et al., Nature, 2006, 441, 861) towards the generation of cyclohexene carbaldehyde...

The preparation of fairly strained carbocyclic ring systems by intramolecular 5-exo-trig ring closure has been well documented, and the absence of proton transfers that would compromise such cyclizations is a hallmark of this chemistry. In an effort to explore the limitations of this approach to more highly strained systems, the preparation of a stellane (tricyclo[3.3.0.0(3,7)]octane) framework...

A unified synthetic strategy toward caged Garcinia natural products has been designed and implemented. Central to the strategy is a tandem Claisen/Diels-Alder/Claisen rearrangement of a suitably substituted xanthone precursor to form forbesione (1a). Serving as a template, forbesione is then used to deliver representative members of this family, including desoxygaudichaudione A (4), desoxymorel...

An organocatalytic quadruple cascade initiated by a Friedel-Crafts-type reaction is described. The (S)-diphenylprolinol trimethylsilyl ether catalyzed reaction yields highly functionalized cyclohexenecarbaldehydes bearing a 1,1-bis[4-(dialkylamino)phenyl]ethene moiety and three contiguous stereogenic centers. The reaction tolerates various functional groups and all products are obtained with ve...

Cells can be considered as systems that utilize changes in thermodynamic entropy as information. Therefore, they serve as useful models for investigating the relationships between entropy production and information transmission, i.e., signal transduction. Based on the hypothesis that cells apply a chemical reaction cascade for the most efficient transduction of information, we adopted a coding ...

The synthesis of small rings by functionalization of C(sp(3) )-H bonds remains a great challenge. We report for the first time a copper-catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extr...

Cascade reactions initiated by radical addition to alkynes are synthetically very attractive because they enable access to highly complex molecular skeletons in only few synthetic steps under usually mild conditions. Here we report a general radical cascade reaction of alkynes, N-fluoroarylsulfonimides and alcohols, enabling the efficient synthesis of important α-amino-α-aryl ketones from readi...

TheMAPK signaling cascade is nowadays understood as a networkmodule highly conserved across species. Its main function is to transfer a signal arriving at the plasma membrane to the cellular interior, the nucleus. Current understanding of ’how’ this is achieved involve the notions of ultrasensitivity and bistability which relate to the nonlinear dynamics of the biochemical network, ignoring spa...

Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered ...

New checkable criteria for persistence of chemical reaction networks are proposed, which extend and complement those obtained by the authors in previous work. The new results allow the consideration of reaction rates which are time-varying, thus incorporating the effects of external signals, and also relax the assumption of existence of global conservation laws, thus allowing for inflows (produ...