A marine viral halogenase that iodinates diverse substrates.

Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage. Notably, halogenases have been previously associated with secondary metabolism, tailoring natural products. Exploration of this viral halogenase reveals it capable of regioselective halogenation of a diverse range of substrates with a preference for forming aryl iodide species; this has potential implications for the metabolism of the infected host. Until recently, a flavin-dependent halogenase that is capable of iodination in vitro had not been reported. VirX1 is interesting from a biocatalytic perspective as it shows strikingly broad substrate flexibility and a clear preference for iodination, as illustrated by kinetic analysis. These factors together render it an attractive tool for synthesis.

Synthesis and antiviral properties of spirocyclic [1,2,3]-triazolooxazine nucleosides.

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of ß-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.

Synthesis of the himandrine skeleton.

The hexacyclic himandrine skeleton 5, which is present in the most complex alkaloids of the tropical rain forest tree Galbulimima belgraveana, has been prepared for the first time. The synthesis begins from the known [3.2.1]benzobicyclooctene intermediate 10. Key steps include a Diels-Alder cycloaddition, Curtius rearrangement, Birch reduction, an intramolecular nucleophilic amination, and a palladium-mediated alkene amination. [reaction: see text]