A Ring-Closing Enyne Metathesis Approach to Functionalized Semicyclic Dienes: The Total Synthesis of (-)-Tetrangomycin

• Published in: European journal of organic chemistry Vol. 2014; no. 8; pp. 1684 - 1694
• Main Authors: Moodie, Lindon W. K., Larsen, David S.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.03.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Asymmetric synthesis; Chemistry; Chemistry, Organic; Cycloaddition; Metathesis; Natural products; Physical Sciences; Science & Technology; Total synthesis; FACE SELECTIVITY; ASYMMETRIC-SYNTHESIS; DIELS-ALDER REACTIONS; Metathesis; ALLYLIC HYDROXY GROUP; TERMINAL ALKYNES; Total synthesis; Cycloaddition; Asymmetric synthesis; ANGUCYCLINE ANTIBIOTICS; Natural products; ANTIBIOTICS (+)-RUBIGINONE B-2; STAPHYLOCOCCUS-AUREUS; RUBIGINONES A; ENANTIOSELECTIVE TOTAL-SYNTHESIS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201301627

The angucycline antibiotic (–)‐tetrangomycin was synthesized in 13 steps (11 % overall yield) by using a stereoselective Diels–Alder reaction between a naphthoquinone and a semicyclic diene to construct the benz[a]anthraquinone ring system. The diene intermediates were synthesized through a ring‐closing enyne metathesis reaction. The tertiary alcohol at C‐3 was installed by an asymmetric dihydroxylation reaction. The relative stereochemistry of the dienes was verified by the NMR analyses of the cycloadducts that were obtained from their reaction with N‐phenylmaleimide. Selective aromatization of the B ring was achieved under oxidative conditions. The angucycline natural product (–)‐tetrangomycin was synthesized from diene 37 in three steps by employing a strategy based on the Diels–Alder reaction. The synthesis of 37 was achieved through the ring‐closing enyne metathesis of 13.