Total Synthesis of (-)-Spiroleucettadine

Richard A Lamb; Nicholas S Aberle; Nigel T Lucas; Guillaume Lessene; Bill C Hawkins

doi:10.1002/anie.201708110

Total Synthesis of (-)-Spiroleucettadine

Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14663-14666. doi: 10.1002/anie.201708110. Epub 2017 Oct 20.

Authors

Richard A Lamb¹, Nicholas S Aberle^{2

3}, Nigel T Lucas¹, Guillaume Lessene^{2

3}, Bill C Hawkins¹

Affiliations

¹ Department of Chemistry, University of Otago, Dunedin, 9054, New Zealand.
² The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052, Australia.
³ Department of Medical Biology and Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, 3050, Australia.

PMID: 28960638
DOI: 10.1002/anie.201708110

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 from l-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.

Keywords: hypervalent iodine; marine alkaloids; natural products; oxidation reactions; total synthesis.

Publication types

Research Support, Non-U.S. Gov't