Biotransformation of artemisinin to a novel derivative via ring rearrangement by Aspergillus niger.

Artemisinin is a component part of current frontline medicines for the treatment of malaria. The aim of this study is to make analogues of artemisinin using microbial transformation and evaluate their in vitro antimalarial activity. A panel of microorganisms were screened for biotransformation of artemisinin (1). The biotransformation products were extracted, purified and isolated using silica gel column chromatography and semi-preparative HPLC. Spectroscopic methods including LC-HRMS, GC-MS, FT-IR, 1D and 2D NMR were used to elucidate the structure of the artemisinin metabolites.1H NMR spectroscopy was further used to study the time-course biotransformation. The antiplasmodial activity (IC50) of the biotransformation products of 1 against intraerythrocytic cultures of Plasmodium falciparum were determined using bioluminescence assays. A filamentous fungus Aspergillus niger CICC 2487 was found to possess the best efficiency to convert artemisinin (1) to a novel derivative, 4-methoxy-9,10-dimethyloctahydrofuro-(3,2-i)-isochromen-11(4H)-one (2) via ring rearrangement and further degradation, along with three known derivatives, compound (3), deoxyartemisinin (4) and 3-hydroxy-deoxyartemisinin (5). Kinetic study of the biotransformation of artemisinin indicated the formation of artemisinin G as a key intermediate which could be hydrolyzed and methylated to form the new compound 2. Our study shows that the anti-plasmodial potency of compounds 2, 3, 4 and 5 were ablated compared to 1, which attributed to the loss of the unique peroxide bridge in artemisinin (1). This is the first report of microbial degradation and ring rearrangement of artemisinin with subsequent hydrolysis and methoxylation by A.niger. KEY POINTS: • Aspergillus niger CICC 2487 was found to be efficient for biotransformation of artemisinin • A novel and unusual artemisinin derivative was isolated and elucidated • The peroxide bridge in artemisinin is crucial for its high antimalarial potency • The pathway of biotransformation involves the formation of artemisinin G as a key intermediate.

A Series of Manganese(III) Salen Complexes as a Result of Team-Based Inquiry in a Transnational Education Programme.

The development of a team-based approach to research-led transnational practical chemistry teaching is described in which a team of five Chinese students on an articulated transnational degree programme, supported by a team of academic and technical staff, carried out a study examining the structural chemistry of a series of manganese(III) salen complexes. A series of four crystallographically characterized manganese(III) salen complexes with ancillary carboxylate ligands are reported here. The carboxylate coordination modes range from the bridging syn-anti µ2 -κO : κO' mode observed in the predominant cyclohexanoate and isobutyrate species, to a capping terminal monodentate mode for the adamantanoate species, and an unusual mixture of bridging and terminal coordination modes observed in a second minor phase of the cyclohexanoate species. The variation on extended structures based on the weakly interacting aliphatic backbones may provide a useful basis for further structural studies.