One of the main themes has been the preparation of cross- conjugated cyclopentenones that featured a one-pot conjugate addition Peterson-olefination sequence (see Figure 1). This method enables the rapid construction of compounds related to Δ12,14-15-deoxy-PGJ2, a member of the well-known prostaglandin family of natural products.
These compounds exhibit several interesting biological activities, including the inhibition of NF-kB, and both activation of the heat shock response (mediated by heat-shock proteins) and peroxisome proliferator activated receptor-γ (PPAR-γ). The latter transcription factor is involved in the way the body uses fats and glucose and is the molecular target for a class of drugs marketed for the treatment of type-2 diabetes. We are involved in a programme whose aim is to prepare and evaluate using a high throughput assay a library of cross-conjugated cyclopentenones for their activation of PPAR-γ.
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More recently we have developed an efficient and mechanistically interesting method for the preparation of cyclic aryl amines involving the double reduction of cyclic sulfonamides (Figure 3). Aromatic amines, accessible using this methodology, are structurally related to neurotransmitters like nicotine and dopamine.
We aim to use this reaction for the stereoselective preparation of amino containing alkaloids like lasubine I.
