Synthetic study on zizaane-type sesquiterpenoids

Abstract

The total synthesis of epizizanoic acid (7,7-dimethyl-6-methylenetricyclo[6,2,1,0^1,5]undecane-2α-carboxylic acid) from (+)-3,3-dimethyl-2-methylenenorbornan-1-ylmethanol (XIII) is described. Hydrocyanation of 4-(3,3-dimethyl-2-methylenenorbornan-1-yl)but-3-en-2-one (XV) derived from the alcohol (XIII), followed by ozonolysis and cyclisation, gave 7,7-dimethyl-4-oxotricyclo[6,2,1,0^1,6]undec-5-ene-2-carbonitrile (XVII), which was converted into methyl 5,6-dihydroxy-7,7-dimethyltricyclo[6,2,1,0^1,6]undecane-2-carboxylate (XXIII). The monomethanesulphonate of (XXIII) was submitted to solvolytic rearrangement to afford the 5-epimers of methyl 7,7-dimethyl-6-oxotricyclo[6,2,1,0^1,6]undecane-2-carboxylate, (XXIV) and (XXVa), which have the desired zizaane skeleton. Finally, the epimer (XXVa) was converted into epizizanoic acid (Ib).