KCS

Resiniferatoxin and Kirkinine belong to daphnane orthoesters group of molecules. They consist of tricyclic core structure having tetradecahydrobenzo[e]azulene ring system. Binding of resiniferatoxin (RTX) to the transient receptor potential cation channel subfamily V member 1 (TRPV1) stimulates and then inactivates heat and vanilloid-responsive nerve endings involved in heat and inflammatory pain signaling. RTX causes to become permeable to cations, most particularly the calcium cation; this evokes a powerful irritant effect followed by desensitization and analgesia. Kirkinine has a remarkable neurotrophic activity. It demonstrates nerve growth factor (NGF) like activity at nanomolar concentrations. It effectively promotes neuronal survival against serum deprivation in nanomolar concentrations. As a result, kirkinine and its analogs present very promising therapeutic opportunities against neurodegenerative diseases such as Alzheimer’s. In an attempt to develop a diverted total synthesis program for synthesis of the core structure of resiniferatoxin and kirkinine, we suggest possible synthetic strategies based on [3+4] cycloaddition reactions. Herein, we will report our current progress toward synthesis of the core tricyclic structure of the title compounds.