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      Stereodivergent Total Synthesis of Δ9-Tetrahydrocannabinols

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          Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish

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            Enantio- and diastereodivergent dual catalysis: α-allylation of branched aldehydes.

            An important challenge in asymmetric synthesis is the development of fully stereodivergent strategies to access the full complement of stereoisomers of products bearing multiple stereocenters. In the ideal case, where four products are possible, applying distinct catalysts to the same set of starting materials under identical conditions would in a single step afford any given stereoisomer. Herein, we describe the realization of this concept in a fully stereodivergent dual-catalytic synthesis of γ,δ-unsaturated aldehydes bearing vicinal quaternary/tertiary stereogenic centers. The reaction is enabled by chiral iridium and amine catalysts, which activate the allylic alcohol and aldehyde substrates, respectively. Each catalyst exerts high local stereocontrol irrespective of the other's inherent preference.
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              Polypharmacology - foe or friend?

              Polypharmacology describes the activity of compounds at multiple targets. Current research focuses on two aspects of polypharmacology: (1) unintended polypharmacology can lead to adverse effects; (2) polypharmacology across several disease-relevant targets can improve therapeutic efficacy, prevent drug resistance, or reduce therapeutic-target-related adverse effects. This perspective reviews these interconnected aspects of polypharmacology. The first part discusses the relevance of polypharmacology for the safety of drugs, the mitigation of safety risks, and methods to identify polypharmacological compounds early in the drug discovery process. The second part discusses the advantages of polypharmacology in the treatment of multigenic diseases and infections, and opportunities for drug discovery and drug repurposing. This perspective aims to provide a balanced view on polypharmacology, which can compromise the safety of drugs, but can also confer superior efficacy.
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                Author and article information

                Journal
                Angewandte Chemie
                Angew. Chem.
                Wiley
                00448249
                December 08 2014
                December 08 2014
                October 10 2014
                : 126
                : 50
                : 14118-14121
                Article
                10.1002/ange.201408380
                c07b8528-ce79-4a18-9dba-936ab60e1476
                © 2014

                http://doi.wiley.com/10.1002/tdm_license_1.1

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