813460-81-0Relevant articles and documents
Total Synthesis of (?)-Spiroleucettadine
Lamb, Richard A.,Aberle, Nicholas S.,Lucas, Nigel T.,Lessene, Guillaume,Hawkins, Bill C.
, p. 14663 - 14666 (2017)
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.
Synthesis and Biological Evaluation of (?) and (+)-Spiroleucettadine and Analogues
Badart, Michael P.,Barnes, Emma M.,Cording, Andrew P.,Gilmer, Selena C. L.,Billinghurst, Ian D.,Edupuganti, Veera V. Shivaji R.,Lessene, Guillaume,Bland, Abigail R.,Bower, Rebekah L.,Rana, Zohaib,Ferguson, Scott A.,Opel Reading, Helen K.,Cook, Gregory M.,Rosengren, Rhonda J.,Krause, Kurt L.,Gamble, Allan B.,Ashton, John C.,Hawkins, Bill C.
, p. 1308 - 1315 (2021)
A second-generation enantiospecific synthesis of spiroleucettadine is described. The original reported antibacterial activity was not observed when the experiment was repeated on the synthetic samples; however, significant anti-proliferative activity was uncovered for both enantiomers of spiroleucettadine. Comparison of the optical rotational data and ORD-CD spectra of both enantiomers and the reported spectrum from the natural source have not provided a definitive answer regarding the absolute stereochemistry of naturally occurring spiroleucettadine. Efforts then focussed on alteration at the C-4 and C-5 positions of the slightly more active (?)-spiroleucettadine. Ten analogues were synthesised, with three analogues found to possess similar anti-proliferative profiles to spiroleucettadine against the H522 lung cancer cell line.
NOVEL SPIROCYCLIC COMPOUNDS
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, (2019/02/13)
The present invention relates to new spirocyclic compounds that may be useful in as anti- cancer and anti-microbial agents, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing cancer, and treating or preventing microbial infections.
Strategies, Setbacks, and Successes in the Synthesis of (-)-Spiroleucettadine
Lamb, Richard A.,Lucas, Nigel T.,Lessene, Guillaume,Hawkins, Bill C.
, p. 10120 - 10133 (2018/07/25)
Various strategies toward the synthesis of the marine natural product (-)-spiroleucettadine are described. In the original strategy, a biomimetic inspired oxidation of a 2-imidazoline scaffold uncovered unexpected reactivity, where benzylic oxidation followed by a Baeyer-Villiger reaction was observed. The second generation approach examined oxidative dearomatization of the phenol ring system first, where a competing spirocyclization process was uncovered. Efforts to forge the scaffold via a carbocation mediated benzyl migration were unsuccessful. Highlights of the successful synthesis include two consecutive hypervalent iodine reactions: the first formed the spirocyclic center and the second facilitated installation of an acetate group at the C-5 position to allow for subsequent introduction of the methyl amine side chain.
