Wandless synthesis, ustiloxin

Just as Nathan started his PhD project in Melbourne, Wandless published the second total synthesis of ustiloxin D. The Wandless synthesis employed an AAA approach to the tertiary alkyl-aryl ether 25, but using a simpler substrate (24) than the functionalized isoleucine derivative we had been constructing (8, 9, or 14). Wandless subsequently converted the olefin in the AAA adduct 25 to the p-hydroxyisoleucine residue (i.e., 25—>27, Scheme 4). Though the AAA reaction proceeded with low diastereoselectivity (2 1), and the subsequent conversion of the olefin 25 to the a-amino acid 27 required multiple steps, the hallmark of the Wandless synthesis was the use of an Evans-Suga Al-catalyzed aldol-type reaction to generate the p-hydroxydopa residue... 

The ustiloxins, isolated from the fungus Ustilaginoidea virens associated with rice plants, show antimitotic properties by inhibiting microtubule formation (7S0, 781). Structurally, they are characterized by the presence of two peptide bonds and one tmusual tertiary alkyl-aryl ether connection. The first total synthesis of ustiloxin D (1205) was achieved in 2002 (782) by Joullie et al., followed by a shorter synthesis by Wandless et al. (783, 784). Later on, its synthesis was conducted again (785) along with ustiloxin F (1206) (786) in a more convergent manner than previously by Joullie et al. (Scheme 15.2). 

Tanaka H, Sawayama AM, Wandless TJ (2003) Enantioselective Total Synthesis of Ustiloxin D. J Am Chem Soc 125 6864... 

Sawayama AM, Tanaka H, Wandless TJ (2004) Total Synthesis of Ustiloxin D and Considerations on the Origin of Selectivity of the Asymmetric Allylic Alkylation. J Org Chem 69 8810... 

Subsequent to Wandless s AAA approach to ustiloxin D being published, Joullie reported a second-generation synthesis. JouUie s second-generation route employed Wandless s method to prepare the p-hydroxydopa residue 30, which as explained earher, is close to perfect. To generate the crucial aUcyl-aryl ether, JouUie developed a novel Cu-promoted coupling of the dopa-derived phenol 31 with a o-serine derived aziridine 32. This reaction proceeds with excellent stereocontrol to generate just one diastereomer of the alkyl-aryl ether adduct 33 (Scheme 6). 

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