Synthesis of the 4-aza cyclopentenone analogue of Δ12,14-15-deoxy-PGJ2 and S-cysteine adducts

The synthesis of a series of 4-aza cross-conjugated cyclopentenones, inspired by the natural prostaglandin Δ12,14-15-deoxy-PGJ2 (5) is described. Using the 4-aza cyclopentenone 7, the installation of the α-side chain was performed using N-functionalisation, following a Boc-deprotection. The ω-side chain was then installed through a Baylis-Hillman type aldol reaction with trans-2-octenal. This afforded 11, the aza-analogue of 5. With this prostaglandin analogue in hand, a series of thiol adducts (14-16) were prepared. Included are activities for compounds 11 and 14-16 in relation to inhibition of the transcription factor NF-κB.