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Stereoselective synthesis of tubuvaline methyl ester and tubuphenylalanine, components of tubulysins, tubulin polymerization inhibitors

✍ Scribed by Taku Shibue; Toshihiro Hirai; Iwao Okamoto; Nobuyoshi Morita; Hyuma Masu; Isao Azumaya; Osamu Tamura


Book ID
104096539
Publisher
Elsevier Science
Year
2009
Tongue
French
Weight
561 KB
Volume
50
Category
Article
ISSN
0040-4039

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✦ Synopsis


Synthetic studies of two components of tubulysins, tubulin polymerization inhibitors are described. The highly stereoselective synthesis of tubuvaline methyl ester (2) was accomplished by 1,3-dipolar cycloaddition of nitrone D-6 and acrylic acid derivatives 7 as a key step. The synthesis of tubuphenylalanine (3) was conducted by an aldol reaction of a boron enolate of (S)-4-isopropyl-3-propionyl-2-oxazolidinone (13) with aldehyde 14, readily prepared from phenylalanine, followed by Barton deoxygenation under radical conditions.