Total Synthesis of Nominine

Scheme 1.2 Total synthesis of nominine, first total synthesis of a hetisine alkaloid...

The late stages of the synthesis (Scheme 1.17) proceeded with Wittig methylenation of ketone 144 with Ph3P=CH2 at 70 °C to furnish exocyclic alkene 145 in 77 % yield. Finally, the alcohol was installed via a Se02-mediated allylic hydroxylation [57] of the exocyclic alkene 145 to afford ( )-nominine (1) in 66 % and 7 1 dr. The structure of nominine (1) was verified via an X-ray crystal structure determination, thereby completing the racemic total synthesis of ( )-nominine (1). 

Overall, the racemic synthesis was accomplished in a 15-step sequence with only a single protecting group manipulation and marked the second total synthesis of ( )-nominine (1) (Scheme 1.20) [59], the first having been completed by Muratake and Natsume in 2004 [19]. The asymmetric synthesis of nominine was accomplished in a 16-step sequence in a similar fashion [60]. 

Owing to their high versatility, selectivity and compatibihty with densely functionalized substrates, radical cyclizations are now frequently introduced in retrosynthetic strategies and have aheady led to the total synthesis of various and relevant natural products [3]. Two recent contributions fully illustrate this. Thus, Muratake and Natsume used a 5-exo-trig cyclization of a vinyl radical to provide a congested methylenebicyclo [2.2.2] octane as a key step in the total synthesis of ( )-nominine [4], and Reddy et al. exploited a sim-... 

Synthetic studies of hetisan-t5rpe aconite alkaloids (total synthesis of ( )-nominine) 06Y237. 

Muratake H, Natsume M. Total synthesis of ( )-nominine, a heptacyclic hetisine-type aconite alkaloid. Angew. Chem. Int. Ed. 2004 43 4646 649. 

Peese KM, Gin DY. Asymmetric synthetic access to the heti-sine alkaloids total synthesis of (+)-nominine. Chem. Eur. J. 2008 14 1654-1665. 

In the total synthesis of the hesitine-type aconite alkaloid nominine, the C-ring was constructed by radical cyclization to form 118 from the enyne precursor 117. ° In the first step, the tin radical reacted with alkyne 117 to form a radical that underwent a 6-exo-trig radical cyclization. The resulting radical was trapped by BuaSnH to give a vinyl stannane, which afforded 117 after destannylation with SiOi (Scheme 25.56). 

---