ABSTRACT
Key building blocks for the production of fully synthetic macrolides have been scaled-up in first time pilot plant and kilo-lab campaigns. These building blocks have supported the discovery of new macrolide antibiotics as well as ongoing preclinical studies.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Macrolides/chemical synthesis , Drug Discovery , Drug Industry , Indicators and Reagents , Protein Synthesis Inhibitors/chemical synthesisABSTRACT
To date the prototype Nazarov cyclization of a cross-conjugated pentadienone to the core structure of the rocaglate natural products has not been successful (9 into 12). It has been found that this conversion can be achieved by the use of acetylbromide in excellent yield and results in a strategically very direct route to these antitumor agents.
Subject(s)
Acetates/chemistry , Benzofurans/chemistry , Antineoplastic Agents/pharmacology , Chemistry, Pharmaceutical/methods , Cross-Linking Reagents/chemistry , Cyclization , Models, Chemical , Molecular Structure , Oxygen/chemistry , Plant Extracts/metabolism , StereoisomerismABSTRACT
Treatment of an N-heterocyclic carbene that features two amide groups N-bound to the carbene nucleus with various organic isocyanides afforded a new class of ketenimines in yields of up to 96% (isolated). DFT analyses revealed that the carbene exhibits a unique, low-lying LUMO, which may explain the atypical reactivity observed.
