(-)-Dysiherbaine was isolated from a Micronesian sponge Dysidea herbacea after screening for substances that exhibit potent neurotoxic activity. This amino acid was found to be a selective agonist of non-NMDA type glutamate receptors in CNS. Although the relative structure was determined to be a novel di-amino di-carboxylic acid having a densely substituted pyran ring fused with 2-amino-3-(2'-carboxy-5'-tetrahydrofuranyl)propanoic acid, its absolute structure remains unsolved. (+)-Lycoperdic acid, isolated from the mashroom Lycoperdon perlatum, is the 5'-oxo analogue of 2-amino-3-(2'-carboxy-5'-tetrahydrofuranyl)propanoic acid which is the core structure of dysiherbaine. We describe here a novel enntiocontrolled synthesis of (+)-lycoperdic acid and the first total synthesis of (-)-dysiherbaine based on the strategy involving four major transformations; (i) palladium catalyzed cross-coupling reaction of the organozinc reagent, prepared from a β-iodo alanine derivative, with an alkenyl iodide or triflate, (ii) diastereoselective epoxidation, (iii) acid catalyzed cyclization, (iv) oxidation. The present synthesis of (-)-dysiherbaine allows us to conclude that the absolute configuration of natural dysiherbaine is (2S,4R,6R,7R,8R,9S).
