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

• Published in: Marine drugs 2019-04, Vol.17 (4), p.245
• Main Author: Serra, Stefano
• Format: Article
• Language: English
• Subjects: Alcohol; Alkylation; Biological activity; Biological Products - chemical synthesis; Biological Products - chemistry; Chemistry Techniques, Synthetic - methods; cyclogeranylsulfonylbenzene isomers; dihydropallescensin 2; Enantiomers; Functional groups; furanosesquiterpenes; Furans - chemical synthesis; Furans - chemistry; Isomerism; Isomers; isomicrocionin-3; lipase-mediated resolution; Metabolites; pallescensin 1; pallescensin 2; pallescensone; Procedures; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Stereoisomerism; stereoselective synthesis; Stereoselectivity
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17040245

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 C cyclogeranyl moiety with the C 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.