A General Strategy for the Stereoselective Synthesis of the Furanosesquiterpenes Structurally Related to Pallescensins 1–2

Abstract

Here, we describe a general stereoselective synthesis of the marine furanosesquiterpenes structurally related to pallescensins 1−2. The stereoisomeric forms of the pallescensin 1, pallescensin 2, and dihydropallescensin 2 were obtained in high chemical and isomeric purity, whereas isomicrocionin-3 was synthesized for the first time. The sesquiterpene framework was built up by means of the coupling of the C10 cyclogeranyl moiety with the C5 3-(methylene)furan moiety. The key steps of our synthetic procedure are the stereoselective synthesis of four cyclogeraniol isomers, their conversion into the corresponding cyclogeranylsulfonylbenzene derivatives, their alkylation with 3-(chloromethyl)furan, and the final reductive cleavage of the phenylsulfonyl functional group to afford the whole sesquiterpene framework. The enantioselective synthesis of the α-, 3,4-dehydro-γ- and γ-cyclogeraniol isomers was performed using both a lipase-mediated resolution procedure and different regioselective chemical transformations.

Keywords

• pallescensin 1
• pallescensin 2
• dihydropallescensin 2
• isomicrocionin-3
• pallescensone
• furanosesquiterpenes
• stereoselective synthesis
• lipase-mediated resolution
• cyclogeranylsulfonylbenzene isomers