Solid-phase total synthesis of (-)-apratoxin a and its analogues and their biological evaluation

Takayuki Doi, Yoshitaka Numajiri, Takashi Takahashi, Motoki Takagi, Kazuo Shin-Ya

研究成果: Article査読

34 被引用数 (Scopus)

抄録

Two approaches for the solid-phase total synthesis of apratoxinA and its derivatives were accomplished. In synthetic route A, the peptide was prepared by the sequential coupling of the corresponding amino acids on trityl chloride SynPhase Lanterns. After cleavage from the polymer-support, macrolactamization of 10, followed by thiazoline formation, provided apratoxinA. This approach, however, resulted in low yield because the chemoselectivity was not sufficient for the formation of the thiazoline ring though its analogue 33 was obtained. However, in synthetic route B, a cyclization precursor was prepared by solid-phase peptide synthesis by using amino acids 13-15 and 18. The final macrolactamization was performed in solution to provide apratoxin A in high overall yield. This method was then successfully applied to the synthesis of apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then evaluated. The epimer 34 was as potent as apratoxinA, and O-methyl tyrosine can be replaced by 7-azidoheptyl tyrosine without loss of activity. The 1,3-dipolar cycloaddition of 38 with phenylacetylene was performed in the presence of a copper catalyst without affecting the thiazoline ring. Solid Approach: Two routes for the solid-phase total synthesis of apratoxinA have been described. On the basis of this method, its analogues were synthesized and their biological activity has been evaluated.

本文言語English
ページ(範囲)180-188
ページ数9
ジャーナルChemistry - An Asian Journal
6
1
DOI
出版ステータスPublished - 2011 1 3

ASJC Scopus subject areas

  • 生化学
  • 有機化学

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