Total Synthesis of Graphislactones A, C, D, and H, of Ulocladol, and of the Originally Proposed and Revised Structures of Graphislactones E and F

• Published in: European Journal of Organic Chemistry Vol. 2009; no. 13; pp. 2130 - 2140
• Main Authors: Altemöller, Martina, Gehring, Timo, Cudaj, Judith, Podlech, Joachim, Goesmann, Helmut, Feldmann, Claus, Rothenberger, Alexander
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.05.2009; Wiley; Wiley-VCH
• Subjects: Chemistry; Chemistry, Organic; Cross‐coupling; Dakin reaction; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Lichen meta­bolites; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Polyketides; Preparations and properties; Resorcylic lactones; Science & Technology; Total synthesis; METABOLITES; ACID; NATURAL-PRODUCTS; Resorcylic lactones; Total synthesis; BOTRYTIS; Polyketides; ENDOPHYTIC FUNGUS; Cross-coupling; Dakin reaction; COUPLING REACTION; A-D; Lichen metabolites; MYCOBIONTS; POLYKETIDE BIOSYNTHESIS; DERIVATIVES; Molecular structure; Metabolite; Resorcinol derivatives; Lactone; Oxygen heterocycle; Lichen; Suzuki coupling; Fungi; Polyketide; Cross reaction; Benzenic compound; Aromatic compound; Acetylation; Spectrophotometry; Chemical synthesis; Acylation
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200801278

Graphislactones A–H and the structurally related ulocladol are highly oxygenated resorcylic lactones produced by lichens and fungi. We present total syntheses of graphislactones A, C–F, H and of ulocladol. Graphislactones E, F, and H were synthesized for the first time. The spectra of graphislactones E and F synthesized as the originally proposed structures were not in agreement with published data. Consequently, revised structures for these compounds are proposed, whose correctness is unambiguously proven by total synthesis and comparison of the spectroscopic data. Key steps in all syntheses are Suzuki couplings for the construction of the central biaryl bond and Dakin reactions to supply further hydroxy groups required in these highly oxygenated substrates. Graphislactones A, C, and H, acylated graphislactone D and ulocladol were prepared in 8–11 steps with 7–20 % yield starting with purchasable compounds, where the longest linear sequence consists of 5–9 steps. The syntheses are thus significantly shorter than the previously published syntheses of graphislactones A–D and of ulocladol. Graphislactones E and F were synthesized in 8 steps, where the longest linear sequences consist of 6 and 5 steps, respectively. They were isolated as the respective acetylated compounds with 25 and 10 % yield.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) Concise syntheses of ulocladol and of the lichen metabolites graphislactones A, C–F, and H are presented. NMR spectroscopic data of graphislactones E and F showed that the originally proposed structures were incorrect. Corrected structures matching the published data were synthesized.