Total Synthesis of (−)‐Spiroleucettadine. (20th October 2017)

• Record Type: Journal Article
• Authors: Lamb, Richard A.; Aberle, Nicholas S.; Lucas, Nigel T.; Lessene, Guillaume; Hawkins, Bill C.
• Is Part Of: Angewandte Chemie. Volume 129:Number 46(2017)
• Page Start: 14855
• Page End: 14858
• Publication Date: 2017-10-20
• Subjects: Hypervalente Iodverbindungen -- Meeresalkaloide -- Naturstoffe -- Oxidationen -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201708110
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans ‐fused 5, 5‐bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (−)‐spiroleucettadine by a highly efficient biomimetic approach starting froml ‐tyrosine. One of two key hypervalent‐iodine‐mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure–biological‐activity relationships of these antibacterial compounds.