NOVEL SYNTHESIS OF AGARITINE, A 4-HYDRAZINOBENZYL-ALCOHOL DERIVATIVE OCCURRING IN AGARICACEAE

The 4-hydrazinobenzyl alcohol (3) was prepared (58%) by diisobutylaluminiumhydride reduction of methyl 4-hydrazinobenzoate (4), whereas LiAlH4 or LiBH4 or reduction of 4 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)benzenediazonium 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-{L2-[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).