Step 1
|
|
Ether/THF |
Al2O3 |
|
THF/H2O |
MeONa/MeOH |
|
|
|
K2CO3/acetone |
MeNH2 |
|
MeOH |
LiAlH4 |
|
THF |
The starting material was 2-hydroxyindolenine that had been previously reported by the authors, who derived it from 3-acetonitrindole. Prenylmagnesium bromide was added in excess with ether/THF as the solvent. The reaction was carried out at -78 degrees to give the gringnard reagent a high solubility in the solvent. There were multiple products but for this single synthesis we follow this specific outcome.
Decyanation was conducted in THF for 3-13 hours in the presence of wet-alumina at reflux to acquire the gamma-lactone. A mechanism involving two successive pseudopericyclic [4 + 2] hydration processes has been proposed for the decyanation.
The next process was to remove the N-substituent. KOH in EtOH and HCO2H resulted in decomposition. Heating KOH in EtOH in a sealed tube gave a medium yield. Finally, MeONa/MeOH was used at reflux to give a good yield of the desired product.
The new reactant slowly decomposed at room temperature. Therefore, it was immediately N-alklylated with K2CO3 and prenyl bromide in acetone at reflux.
Debromoflustramide B was formed by the application of methylamine/MeOH at room temperature in a near full yield.
Unlike the other four reactions, LiAlH4 in THF was utilized because the aromatic ring didn't contain the reactive bromide. The final product was analyzed by IR and NMR, showing to be in accordance with natural occurring debromoflustramine B.