Total Synthesis of 1‐Hydroxytaxinine. (25th July 2019)

• Record Type: Journal Article
• Authors: Imamura, Yusuke; Yoshioka, Shun; Nagatomo, Masanori; Inoue, Masayuki
• Is Part Of: Angewandte Chemie. Volume 131:Number 35(2019)
• Page Start: 12287
• Page End: 12291
• Publication Date: 2019-07-25
• Subjects: Naturstoffe -- Radikale -- Tellur -- Terpenoide -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201906872
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 1‐Hydroxytaxinine (1 ) is a cytotoxic taxane diterpenoid. Its central eight‐membered B‐ring possesses four oxygen‐functionalized centers (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six‐membered A‐ and C‐rings. The densely functionalized and intricately fused structure of 1 makes it a highly challenging synthetic target. Reported here is an efficient radical‐based strategy for assembling 1 from A‐ and C‐ring fragments. The A‐ring bearing an α‐alkoxyacyl telluride moiety underwent intermolecular coupling with the C‐ring fragment by a Et3 B/O2 ‐promoted decarbonylative radical formation. After construction of the C8‐quaternary stereocenter, a pinacol coupling reaction using a low‐valent titanium reagent formed the B‐ring with stereoselective installation of the C1, C2‐diol. Subsequent manipulations at the A‐ and C‐rings furnished 1 in 26 total steps. Abstract : ABC : 1‐Hydroxytaxinin, ein cytotoxisches Taxan‐Diterpenoid, enthält ein hoch oxygeniertes 6/8/6‐gliedriges Ringsystem (ABC‐Ringsystem). Eine decarbonylierende intermolekulare Radikalkupplung und eine durch niedervalentes Titan geförderte intramolekulare Radikalcyclisierung sind die Schlüsselreaktionen zur Anellierung des B‐Rings ausgehend von A‐ und C‐Ringfragmenten. Nachfolgende Manipulationen an den A‐ und C‐Ringen ergeben 1‐Hydroxytaxinin in 26 Stufen.