ABSTRACT
A metal-free, user-friendly photochemical transformation of nitroalkanes to oximes, nitrones, and hydroxylamines has been developed. The visible-light-induced reactions are catalyzed by the readily available photoredox organocatalyst 4CzIPN and use inexpensive amines as reductants. Broad in scope and tolerant of multiple functional groups and heterocycles, the transformation proceeds under mild conditions. Its synthetic potential was demonstrated in the formal total synthesis of amathaspiramide F. A basic insight into the reaction mechanism was gained with the help of an NMR study.
ABSTRACT
The first total synthesis of the potent antibiotic berkeleylactone A is described in 10 steps with an overall yield of 9.5%. A key step of our concise route is a late-stage, highly diastereoselective, sulfa-Michael addition. The 16-membered macrocyclic lactone was formed via ring closing metathesis and subsequent chemoselective reduction. The absolute stereochemical configuration was confirmed by single-crystal X-ray analysis. Synthetic berkeleylactone A was tested against several methicillin-resistant Staphylococcus aureus strains, and its potent antibacterial activity was verified.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Macrolides/chemical synthesis , Macrolides/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Crystallography, X-Ray , Macrolides/chemistry , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
Crystallization-induced diastereomer transformation (CIDT) represents a highly appealing and convenient synthetic tool. Despite its numerous advantages, it remains rather rarely used due to its uncertain predictability to occur. Herein, we describe CIDT based on aza-Michael reactions of diversely functionalized ( E)-3-acylacrylic acids. This method provides direct access to a broad variety of α-amino acid derivatives in excellent stereochemical purities.