Total synthesis acutumine

Scheme 10 Radical cyclization as key step in the total synthesis of acutumine (26) [75]...

In all the following examples, the targeted double bonds were activated by suitable substituents to increase the efficacy of the desired cyclization mode. For the total synthesis of acutumine (26), an activated a,p-unsaturated ketone 27 was chosen as precursor (Scheme 10) [74, 75], Aryl radical additions to this type of alkenes are known to proceed about ten times faster than to comparable allylic alcohols. In a radical-polar crossover reaction, the spirocyclic product 28 was obtained in the presence of triethylaluminum as promoter and an oxaziridine as hydroxylating agent. The fact that even the efficient hydrogen donor tetrahydrofuran could be used as solvent nicely demonstrates the high efficacy of the cyclization step. 

Total Synthesis of (-)-Acutumine Castle and co-workers reported on the first total synthesis of (—)-acu-tumine 147 in 2009. " Isolated from Sinomenium acutum by Goto and Sudzuki in 1929, " this tetracyclic alkaloid is noted for its unique structural features that include a spiro-cyclic propellane-type system. This molecule also offers useful biological activities such as selective T-cell cytotoxicity and anti-amnesic properties. The synthetic route started from easily synthesizable starting materials chiral 143 and 144 to generate the precursor 145. The key step of the synthesis involves a one-pot ozonolysis-reductive amination on 145 to afford 146 (Scheme 39.43). 

SCHEME 39.43. One-pot ozonolysis—reductive amination protocol for the total synthesis of (—)-acutumine. 

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