Novel Synthesis of Agaritine, a 4-Hydrazinobenzyl-Alcohol Derivative Occurring in Agaricaceae

The 4‐hydrazinobenzyl alcohol (3 was prepared (58%)) by diiobutylaluminiumhydride reduction of methyl 4‐hydrazinobenzoate (4), whereas LiA1H4 or LiBh4 reduction of4 proceeded further to yield (via intermediate 3) (4‐tolyl)hydrazine (5). The alcohol 3 was stable under O2‐free conditions and exhibited no tendency to eliminate H2O, neither thermally nor with H+ catalysis. Oxidation of 3 with SeO2 yielded 4‐(hydroxymethyl)benzine‐diazonium ion (8), identified by its azo coupling product 9 with 2‐naphthol. Condensation of 3 with 1‐benzyl 5‐Hydrogen N‐(benzyloxycarbonyl)‐L‐glutamate (10) in presence of dicyclohexylcarbodiimide afforded 81% of N2‐(benzyloxycarbonyl)‐L‐ glutamic acid 1‐(benzyl‐ester) 5‐{2‐[4‐(hydroxymethyl)phenyl]hydrazide} (11) which upon controlled hydrogenolysis (quinoline‐sulfur‐poisoned Pd/C catalyst) gave 82% of L‐Glutamic acid 5‐{2‐[4‐(hydroxymethyl)phenyl] hydrazide} (1), i. e. agaritine, a metabolite of Agaricus bisporus. Without poisoning of the catalyst, hydrogenolysis of (11) yielded L‐glutamic acid 5‐[2‐(4‐tolyl)hydrazide] (12).