ENANTIOSELECTIVE FORMAL SYNTHESIS OF ACROMELIC ACID-A VIA TANDEM MICHAEL REACTION METHODOLOGY

A new formal synthesis of the potent neurotoxin, acromelic acid A, has been accomplished by a tandem Michael reaction involving the 2-nitro- 1,3-diene 4, incorporated into a dihydropyridone nucleus, as electroph ilic alkene and the beta,gamma-unsaturated glutamic ester derivative 1 , prepared from D-serine, as a tool for the stereoselective constructi on of the key 2,3,4-trisubstituted pyrrolidine ring system. After havi ng served its stereocontrolling role, the allylic nitro group was remo ved regio- and stereoselectively by hydride transfer reaction in the p resence of a palladium catalyst, which proceeded with concomitant dehy drogenation of the side-chain heterocycle. The completion of the forma l synthesis of the natural target required adjustement of the oxidatio n level of the functional group at the carbon adjacent to the pyrrolid ine nitrogen and selective removal of the pyridone nitrogen protective group.