Enantioselective Total Synthesis of (–)‐Siphonodictyal B and (+)‐8‐epi‐Siphonodictyal B with Phosphatidylinositol 3‐Kinase α (PI3Kα) Inhibitory Activity. Issue 34 (2nd November 2016)

• Record Type: Journal Article
• Authors: Kikuchi, Takuya; Narita, Koichi; Saijo, Ken; Ishioka, Chikashi; Katoh, Tadashi
• Is Part Of: European journal of organic chemistry. Issue 34(2016)
• Page Start: 5659
• Page End: 5666
• Publication Date: 2016-11-02
• Subjects: Natural products -- Total synthesis -- Terpenoids -- Polyketides -- Biological activity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201600949
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : The biologically interesting marine meroterpenoids (–)‐siphonodictyal B and (+)‐8‐ epi ‐siphonodictyal B were efficiently synthesized in 29–40 % overall yield in a longest linear sequence of 11 steps, starting from commercially available (+)‐sclareolide. The synthesis involved the following crucial steps: (i) stereodivergent hydrogenation of a homoallylic decalin alcohol to install the requisite C8 stereogenic centre present in the decalin fragments; (ii) coupling of the decalin fragments with an aromatic moiety to assemble the desired carbon skeletons; and (iii) deprotection from multiple O ‐protective groups on the aromatic ring to complete the project synthesis. Both (–)‐siphonodictyal B and (+)‐8‐ epi ‐siphonodictyal B showed PI3Kα inhibitory activity, with potencies comparable to that of liphagal, a naturally occurring PI3Kα inhibitor. New structure–activity relationships for this class of marine meroterpenoids were also revealed. Abstract : (–)‐Siphonodictyal B and (+)‐8‐ epi ‐siphonodictyal B were synthesized in 29–40 % overall yield in a longest linear sequence of 11 steps, starting from commercially available (+)‐sclareolide. The synthesized compounds showed PI3Kα inhibitory activity at potencies comparable to that of (+)‐liphagal, a naturally occurring PI3Kα inhibitor.