Enantioselective Total Synthesis of Ustiloxin D
- 14 May 2003
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 125 (23), 6864-6865
- https://doi.org/10.1021/ja035429f
Abstract
Ustiloxin D and phomopsin A are potent antimitotic agents that bind to tubulin and interfere with cellular microtubule function. A synthetic strategy has been developed to allow access to both of the natural products as well as a variety of variants of the ustiloxin and phomopsin family members in order to provide sufficient quantities for biological studies. Herein we report the enantioselective total synthesis of ustiloxin D using a longest linear sequence of 20 steps. Four of the five stereocenters were set using catalytic asymmetric methodologies. In particular, Evans's new Al-catalyzed asymmetric aldol reaction facilitated access to both syn and anti products corresponding to the different benzylic stereochemistries found in ustiloxins and phomopsins. In addition, due to its high functional group tolerance, Trost's Pd-mediated etherification was used to construct the chiral tertiary alkyl−aryl ether. Taken together, these synthetic strategies allow us to use densely functionalized intermediates to realize an efficient synthesis of ustiloxin D.This publication has 11 references indexed in Scilit:
- A New Approach to Osmium-Catalyzed Asymmetric Dihydroxylation and Aminohydroxylation of OlefinsAngewandte Chemie, 2002
- Efficient Synthesis of β,γ-DehydrovalineThe Journal of Organic Chemistry, 1999
- A Stereospecific Elimination to Form Dehydroamino Acids: Synthesis of the Phomopsin Tripeptide Side ChainJournal of the American Chemical Society, 1999
- A Simple and Efficient Method for the Preparation of Hindered Alkyl−Aryl EthersThe Journal of Organic Chemistry, 1998
- Synthesis and Anti-tubulin Activity of Ustiloxin D Derivatives.The Journal of Antibiotics, 1998
- A Synthetic Approach towards the Identification of Periplaneta Sex PheromonesHETEROCYCLES, 1998
- Ustiloxins, antimitotic cydic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens.The Journal of Antibiotics, 1994
- Improved enantioselectivity in asymmetric dihydroxylations of terminal olefins using pyrimidine ligandsThe Journal of Organic Chemistry, 1993
- Antimitotic agents: Chemistry and recognition of tubulin moleculeMedicinal Research Reviews, 1993
- Ustiloxin: a phytotoxin and a mycotoxin from false smuth balls on rice paniclesTetrahedron Letters, 1992