Studies Directed toward the Synthesis of Ulapualide A. Asymmetric Synthesis of the C8-C25 Tris-Oxazole Fragment

摘要

The first asymmetric synthesis of a suitably functionalized tris-oxazole fragment, identical to those of the ulapualides and with general application to the entire class of natural products, was accomplished in a convergent manner using 11 steps in 12% overall yield. An iterative Hantzsch-oxazole protocol was developed for the synthesis of the bis-oxazole subunit, while a new application of our chiral silane bond construction methodology was employed for the asymmetric synthesis of the chiral amine subunit. This chemistry played a key role in the synthesis of the third oxazole ring containing the methyl-bearing side chain. The coupling of the C26-C42 fragment described in the preceding paper to the tris-oxazole fragment and completion of the synthesis of ulapualide A will be reported at a later time.