Asymmetric Syntheses and Wnt Signal Inhibitory Activity of Melleumin A and Four Analogues of Melleumins A and B

作者：Luo, Jie-Min; Dai, Chao-Feng; Lin, Shu-Yong; Huang, Pei-Qiang^*

来源：Chemistry-An Asian Journal, 2009, 4(2): 328-335.

DOI：10.1002/asia.200800355

• asymmetric synthesis
• biological activity
• natural products
• total synthesis
• Wnt signal inhibition

The first total synthesis of melleumin A and four analogues of melleumins A and B is described. The N-acyl L-Thr-Gly/beta-hydroxy-gamma-amino acid coupling/macrolactamization strategy allowed the efficient assembly of the three segments being free of epimerization. While the Jouin-Castro method with minor modification allows a rapid entrance to the key syn-beta-hydroxy-gamma-amino acid segment, required for the synthesis of melleumin A, an extension of our malimide-based methodology using a changed N-protecting group affords a flexible access to several anti-beta-hydroxy-gamma-amino acids, and hence analogues of melleumins A and B. Among them, unnatural 4-epi-melleumin B (2a) exhibits a modest inhibitory activity on Wnt signaling. The total synthesis of melleumin A allowed confirmation of its full structure.

• 出版日期2009
• 单位厦门大学