The synthesis of pantherine and related compounds

Abstract

One of the active principles of Amanita muscaria, 5-aminomethyl-3-hydroxyisoxazole (I) has been synthesised from 3-bromo-5-methylisoxazole by way of 3-methoxyisoxazole-5-acetic acid (XIII), and from 3-methoxyisoxazole-5-carboxylic acid (XXa) by reduction of its amide with diborane. Analogues of (I) with methyl and ethyl substituents in the 4-position have been prepared similarly from 3-hydroxy-4,5-dimethylisoxazole and 4-ethyl-3-hydroxy-5-methylisoxazole by the first method. Homologues of (I) with longer basic side chains in the 5-position were made by the Curtius reaction from 3-methoxyisoxazole-5-propionic acid (XXIIb), and by diborane reduction of amides of 3-methoxyisoxazole-5-acetic acid (XIII) and 3-methoxy-4-methylisoxazole-5-acetic acid (XXIb). 3-Hydroxyisoxazoles with the basic side chain in the 4-position were prepared from 3-hydroxy-5-methylisoxazole-4-carboxylic acid (XXXIIb) and ethyl 2-(trifluoroacetamidomethyl) acetoacetate (XXV).