Biogenetically Inspired Total Synthesis of (+)‐Liphagal: A Potent and Selective Phosphoinositide 3‐Kinase α (PI3Kα) Inhibitor from the Marine Sponge Aka coralliphaga1. Issue 16 (17th April 2014)

• Record Type: Journal Article
• Authors: Kamishima, Takaaki; Kikuchi, Takuya; Narita, Koichi; Katoh, Tadashi
• Is Part Of: European journal of organic chemistry. Issue 16(2014)
• Page Start: 3443
• Page End: 3450
• Publication Date: 2014-04-17
• Subjects: Natural products -- Total synthesis -- Enzymes -- Inhibitors -- Terpenoids -- Liphagal; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402082
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A biologically attractive and structurally unique marine natural product, (+)‐liphagal, was biomimetically synthesized in 29 % overall yield in a longest linear sequence of 13 steps from commercially available (+)‐sclareolide. This synthesis involved the following crucial steps: (i) stereocontrolled hydrogenation of an endo ‐olefinic decalin to install the C8 stereogenic centre present in the requisite decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; (iii) ring expansion of a proposed biogenetic intermediate followed by benzofuran formation to establish the requisite tetracyclic core structure. A few new aspects of the proposed biosynthetic pathway to this class of natural products were revealed. Abstract : (+)‐Liphgal, a biologically attractive and structurally unique marine natural product, was synthesized in 29 % overall yield in a longest liner sequence of 13 steps from commercially available (+)‐sclareolide. A characteristic tetracyclic core structure was established by a method based on the proposed biosynthetic pathway.