ABSTRACT
Indole alkaloids are a diverse class of natural products known for their wide range of biological activities and complex chemical structures. Rarely observed in this class are indolic nitrones, such as avrainvillamide and waikialoid, which possess potent bioactivities. Herein the oxa gene cluster from the marine-derived fungus Penicillium oxalicum F30 is described along with the characterization of OxaD, a flavin-dependent oxidase that generates roquefortine L, a nitrone-bearing intermediate in the biosynthesis of oxaline. Nitrone functionality in roquefortine L was confirmed by spectroscopic methods and 1,3-dipolar cycloaddition with methyl acrylate. OxaD is a versatile biocatalyst that converts an array of semisynthetic roquefortine C derivatives bearing indoline systems to their respective nitrones. This work describes the first implementation of a nitrone synthase as a biocatalyst and establishes a novel platform for late-stage diversification of a range of complex natural products.
Subject(s)
Indoles/chemistry , Nitrogen Oxides/chemistry , Nitrogen Oxides/metabolism , Oxygenases/metabolism , Penicillium/enzymology , Biocatalysis , Heterocyclic Compounds, 4 or More Rings/metabolism , Imidazoles/metabolism , Indoles/metabolism , Multigene Family/genetics , Oxidation-Reduction , Penicillium/genetics , Piperazines/metabolismABSTRACT
Commercial application of many promising heterocyclic natural products is limited by their natural abundance. While organic synthesis provides access to many natural products, total synthesis of numerous complex molecules is not economically feasible. In recent years, the combination of fermentation and organic synthesis has provided a new route for the production of complex heterocycles that are inaccessible by typical synthetic methods. This JOCSynopsis will review examples of how this union of disciplines has overcome obstacles in both academia and industry.
Subject(s)
Fermentation , Heterocyclic Compounds/chemical synthesis , Organic Chemicals/chemical synthesis , Biological Products/chemical synthesis , Biological Products/metabolismABSTRACT
Natural products bearing a triazaspirocyclic motif have received significant attention in recent years. These compounds, which feature three nitrogen atoms attached to one quaternary carbon forming a spirocyclic scaffold, exhibit a wide range of biological activity and have promising applications in materials as well as in drug discovery. In this review article, we will discuss triazaspirocycles in Nature, their biological activity, and applications. Methods for the synthesis of triazaspirocycles as well as the reactivity of triazaspirocyclic scaffolds will be reviewed.
ABSTRACT
The reaction of aliphatic and aromatic isonitriles with sulfuryl chloride provides an efficient, general route to the corresponding dichlorides without byproducts of free-radical substitution.
