Total Synthesis of (-)-Lepadin F based on a stereoselective Diels-Alder reaction controlled by a ketolactone-type dienophile.

An effcient approach to the type III lepadin alkaloids (lepadins F and G) has been developed via a key Diels-Alder reaction, in which a novel ketolactone-type dienophile with chiral diol unit is employed to generate the desirable all-cis-trisubstituted cyclohexene in excellent regio- and stereoselectivity control. The subsequent selective sulfonylation of the diol unit followed by S N 2 cyclization under hydrogenation conditions could construct the substituted piperidine ring. By the approach, (-)-lepadin F is synthesized from ethyl L-lactate for the first time.