Adriadysiolide,the First Monoterpenoid Isolated from a Marine Sponge

Spectra and chemical transformations allow to establish the gross structure 6,7-epoxy-4,7-dimethyl-l-oxa-spiro4.4]non-3-en-2-one for adriadysiolide ( 1 ), the first monoterpenoid isolated from a marine sponge, a Dysidea sp. of the Adriatic Sea. Its configuration 5R*, 6S*, 7S* as given in 1a is derived from diastereoselective total syntheses of both 1a and its diastereoisomer 1b via stereochemically predictable peracid epoxidations of olefinic precursors. Thus, OH assistance in allylic alcohol 8 leads to oxirane 13 which is subjected to methyl cuprate conjugate addition to give epiadriadysiolide ( 1b ), whilst electronic deactivation by a neighboring heterocyclic O-atom in intermediate 5 , derived from 8 mainly leads to adriadysiolide ( 1a ). Comparative ¹H-NMR shift-reagent effects with 1a and 1b , evaluated with the aid of molecular-mechanics calculations, support these conclusions.