Total synthesis of bioactive natural product Curzerene

Abstract:

Curzerene is a natural product of terpene furans isolated from the curcuma rhizomes, which has various biological activities such as anti-inflammation, anti-cancer and anti-leishmaniasis. In this paper, commercially available (+)-verbenone (6) was utilized as chiral starting material to synthesize Curzerene in 5 steps with 34% total yield. A key ketone compound 4 was first obtained through a known three-step reaction. Then ketone 4 and 1,1-dimethoxyacetone underwent TiCl4-Et3N-mediated cyclization reaction to afford natural products isogermafurenolid (2) and its isomer 8-epi-isogermafurenolid (2′) in 56% and 20% yield, respectively. Finally, the target Curzerene was synthesized from 2 and 2′ with 82% yield by a one-pot reaction of DIBAL-H reduction and subsequent acid promoted dehydration.