Total synthesis of eudesmane terpenes by site-selective C-H oxidations

• Published in: Nature (London) 2009-06, Vol.459 (7248), p.824-828
• Main Authors: Chen, Ke, Baran, Phil S
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkenes; Biological Products - chemical synthesis; Biological Products - chemistry; Biomimetics; Biosynthesis; Carbon - chemistry; Chemical synthesis; Chemistry; Exact sciences and technology; Hormones; Humanities and Social Sciences; Hydrogen - chemistry; letter; Mass spectrometry; Molecular Structure; Molecular weight; multidisciplinary; Natural products; Organic chemistry; Organic compounds; Oxidation; Oxidation-Reduction; Oxidation-reduction reaction; Physiological aspects; Preparations and properties; Science; Science (multidisciplinary); Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes, Eudesmane - chemical synthesis; Sesquiterpenes, Eudesmane - chemistry; Steroids; Synthesis; Terpenes
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature08043

From menthol to cholesterol to Taxol, terpenes are a ubiquitous group of molecules (over 55,000 members isolated so far) that have long provided humans with flavours, fragrances, hormones, medicines and even commercial products such as rubber. Although they possess a seemingly endless variety of architectural complexities, the biosynthesis of terpenes often occurs in a unified fashion as a 'two-phase' process. In the first phase (the cyclase phase), simple linear hydrocarbon phosphate building blocks are stitched together by means of 'prenyl coupling', followed by enzymatically controlled molecular cyclizations and rearrangements. In the second phase (the oxidase phase), oxidation of alkenes and carbon-hydrogen bonds results in a large array of structural diversity. Although organic chemists have made great progress in developing the logic needed for the cyclase phase of terpene synthesis, particularly in the area of polyene cyclizations, much remains to be learned if the oxidase phase is to be mimicked in the laboratory. Here we show how the logic of terpene biosynthesis has inspired the highly efficient and stereocontrolled syntheses of five oxidized members of the eudesmane family of terpenes in a modicum of steps by a series of simple carbocycle-forming reactions followed by multiple site-selective inter- and intramolecular carbon-hydrogen oxidations. This work establishes an intellectual framework in which to conceive the laboratory synthesis of other complex terpenes using a 'two-phase' approach.