Total synthesis of the assigned structure of (+)-Maneolactenol

Abstract

The first total synthesis of the assigned structure of (+)-maneolactenol, a marine natural product, has been completed in 7 steps. The pivotal transformations involve an asymmetric Diels-Alder reaction which serves as a key step in establishing stereochemistry, and the formation of core skeleton through iodolactonization. Particularly noteworthy are the selective reduction of acid to aldehyde and subsequent chelation-controlled stereoselective nucleophilic addition, facilitating the rapid and efficient assembly of side-chain motifs, as well as the selective reduction of the triple bond to Z-olefin moiety for the side chain construction. This strategy enabled the scalable synthesis of over 100 mg of the target compound, highlighting its practicality for larger-scale production.