Synthesis edit
Aconitine is naturally synthesized by the monkshood plant via the terpenoid biosynthesis pathway (MEP chloroplast pathway). [1] Approximately 700 naturally occurring C19-diterpenoid alkaloids have been isolated and identified, but the synthesis of only a few of these alkaloids are well understood.[2] In 1971, the Weisner group discovered the total synthesis of talatisamine (a C19-norditerpenoid). [3] In the subsequent years, they also discovered the total syntheses of other C19-norditerpenoids, such as chasmanine [4],[5] and 13-deoxydelphonine. [6]
The total synthesis of napelline (Scheme a) begins with aldehyde 100. [7] In a 7 step process, the A-ring of napelline is formed (104). It takes another 10 steps to form the the lactone ring in the pentacyclic structure of napelline (106). An additional 9 steps creates the enone-aldehyde 107. Heating in methanol with potassium hydroxide causes an aldol condensation to close the sixth and final ring in napelline (14). Oxidation then gives rise to diketone 108 which was converted to (±)-napelline (14) in 10 steps.
A similar process is demonstrated in Wiesner’s synthesis of 13-desoxydelphinone (Scheme c).[8] The first step of this synthesis isthe generation of a conjugated dienone 112 from 111 in 4 steps. This is followed by the addition of a benzyl vinyl ether to produce 113. In 11 steps, this compound is converted to ketal 114. The addition of heat, DMSO and o-xylene rearranges this ketol (115), and after 5 more steps (±)-13-desoxydelphinone (15) is formed.
Lastly, talatisamine (Scheme d) is synthesized from diene 116 and nitrile 117.[9] The first step is to form tricycle 118 in 16 steps. After another 6 steps, this compound is converted to enone 120. Subsequently, this allene is added to produce photoadduct 121. This adduct group is cleaved and rearrangment gives rise to the compound 122. In 7 steps, this compound forms 123, which is then rearranged, in a similar manner to compound 114, to form the aconitine-like skeleton in 124. A racemic relay synthesis is completed to produce talatisamine (13).
- ^ Viberti, Fabrizio; Raveggi, Elisa. "ACONITINE: HOW POISONOUS, HOW HARMFUL?". flipper e nuvola. Retrieved 26 April 2017.
- ^ Zhao P-J, Gao S, Fan L-M, Nie J-L, He H-P, Zeng Y, Shen Y-M, Hao X-J. J. Nat. Prod. 2009;72:645–649.
- ^ Synthesis: Wiesner K, Tsai TYR, Huber K, Bolton SE, Vlahov R. J Am Chem Soc. 1974;96:4990–4992.
- ^ Wiesner K, Tsai TYR, Nambiar KP. Can J Chem. 1978;56:1451–1454.
- ^ Tsai TYR, Tsai CSJ, Sy WW, Shanbhag MN, Liu WC, Lee SF, Wiesner K. Heterocycles. 1977;7:217–226.
- ^ Wiesner K. Pure Appl Chem. 1979;51:689–703.
- ^ Synthesis: Wiesner K, Tsai TYR, Huber K, Bolton SE, Vlahov R. J Am Chem Soc. 1974;96:4990–4992.
- ^ Wiesner K, Tsai TYR, Nambiar KP. Can J Chem. 1978;56:1451–1454.
- ^ Wiesner K. Pure Appl Chem. 1979;51:689–703.