- Evolution of the total syntheses of ustiloxin natural products and their analogues
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Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an SNAr reaction. An NOE study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F, and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R,10S)-epi-ustiloxin analogues) were prepared via the second-generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization.
- Li, Pixu,Evans, Cory D.,Wu, Yongzhong,Cao, Bin,Hamel, Ernest,Joullie, Madeleine M.
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p. 2351 - 2364
(2008/09/20)
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- A convergent total synthesis of ustiloxin D via an unprecedented copper-catalyzed ethynyl aziridine ring-opening by phenol derivatives
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(Chemical Equation Presented) The ustiloxins are a family of heterodetic cyclopeptides that have been isolated from the water extracts of false smut balls on the panicles of rice plants caused by the fungus Ustilaginoidea virens. A concise total synthesis of ustiloxin D has been achieved via an unprecedented ethynyl aziridine ring-opening of phenol derivatives. The longest linear sequence of the synthesis is 15 steps from commercially available compounds.
- Li, Pixu,Evans, Cory D.,Joullie, Madeleine M.
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p. 5325 - 5327
(2007/10/03)
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- Total synthesis of ustiloxin D and considerations on the origin of selectivity of the asymmetric allylic alkylation
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As part of investigations into cell cycle checkpoint inhibitors, an asymmetric synthesis of the antimitotic natural product, ustiloxin D, has been completed. A salen-Al-catalyzed aldol reaction was employed to construct a chiral oxazoline 9 (99% yield, 98
- Sawayama, Andrew M.,Tanaka, Hiroko,Wandless, Thomas J.
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p. 8810 - 8820
(2007/10/03)
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