Organic & Biomolecular Chemistry Blog

This Communication by Marco Bella et al. is a study of the historically famous Rabe amination, presenting preliminary results for a “modern” organocatalytic version of the reaction whereby direct functionalisation of ketones and aldehydes with N-chloro amines is achieved in mild conditions. Bella et al. also report that when aldehydes bearing a CH₂ moiety in the α-position are used, a novel rearrangement is observed leading to α-amino ketones.

Have a look at the Communication for more details on the experimental procedure and possible mechanistic explanation for this interesting reaction, it’s free to access for 4 weeks!

The Rabe amination after a century: direct addition of N-heterocycles to carbonyl compounds
Daniele M. Scarpino Schietroma, Mattia R. Monaco, Valerio Bucalossi, Philipp E. Walte, Patrizia Gentili and Marco Bella
DOI: 10.1039/C2OB25595B

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) administered as a first-line treatment against HIV. Despite its efficacy, a major shortcoming is its association with toxic events. The reasons for the drug’s adverse effects are not currently clear, but in order to answer this question the availability of considerable amounts of enantiomerically pure EFV metabolites is essential, to allow in vitro and in vivo toxicological studies.

In this Hot paper Alexandra M. M. Antunes and co-workers report the development of a method for the direct aromatic hydroxylation of EFV, and other xenobiotics, using the easily accessible [Fe^II(bpmen)(OTf)₂]–H₂O₂ oxidant system in the presence of acetic acid. Antunes et al. say that “This cost-efficient one-pot strategy represents a considerable improvement when compared with the already available methods for the C8 hydroxylation of EFV, avoiding a laborious multi-step synthetic approach and the resolution of racemic mixtures.”

In addition to EFV, Antunes et al. successfully oxidise tamoxifen and equilin into their phenolic metabolites which demonstrates the general application of bio-inspired nonheme Fe-complexes for in vitro access to phenolic species typically formed via cytochrome P450 (CYP)-mediated hydroxylation of aromatic compounds. The possibility of applying an oxidation system mirroring the CYP metabolic pathways predicts the usefulness of the approach for molecular toxicology studies of a large variety of toxic aromatic xenobiotics.

This work represents a proof of concept regarding bio-inspired oxidation technologies and opens new opportunities for this chemistry. To find out more read the article in full here.

This paper will be free to access for the next 4 weeks.

Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz
Riccardo Wanke, David A. Novais, Shrika G. Harjivan, M. Matilde Marques and Alexandra M. M. Antunes
Org. Biomol. Chem., 2012,
DOI: 10.1039/C2OB25212K