One-pot synthesis and negative ion mass spectrometric investigation of a densely functionalized cinnoline, 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile

Known densely substituted 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile was synthesized using a new synthetic protocol involving chloranil and malonitrile via quinone methide formation. This one-pot synthesis occurs under base mediated conditions in a polar medium. The method involves condensation of excess malononitrile with chloranil in ethanol at reflux to 2-(2,4,5-trichloro-3-hydroxy-6-oxocyclohexa-2,4-dien-1-ylidene) malononitrile. This is an atom efficient, simple and effective procedure for the preparation of a highly substituted cinnoline that can serve as a relay to antimalarial prototypes

Purpurogallin-A heme binding component of oak galls

Recently, it has been shown that Purpurogallin (PPG), an orange benztropolone constituent of oak galls and its derivative, CU-CPT22, can compete with the binding of the specific lipoprotein ligand to toll-like receptors (TLRs), which are type I transmembrane proteins. These recognize pathogen-derived macromolecules that play a key role in the innate immune system. This system provides an attractive target for the treatment of various immune disorders. Notably, PPG also interacts with various metals and its mode of action against HIV in vitro may involve inhibition of metal containing integrases. In the current study, an optimised synthesis of PPG is presented together with its gas phase behaviour (probed by mass spectrometry) as well as its redox behaviour with porphyrins such as heme. This interaction may also explain its effects at metal containing integrases within HIV in vitro as well as its action during processing of iron complexes within Plasmodia. This compound could serve as a novel prototype for the synthesis of novel redox active antimalarials