P-30 海綿由来血管新生阻害物質cortistatin Aおよびanalog化合物の合成研究(ポスター発表の部)

DOI

書誌事項

タイトル別名
  • P-30 Synthetic Studies and Biological Evaluation of Cortistatin A, an Anti-Angiogenic Steroidal Alkaloid from Marine Sponge, and Its Analogs(Poster Presentation)

抄録

We have isolated cortistatins, novel steroidal alkaloids having anti-angiogenic property, from the marine sponge Corticium simplex in 2006. Among them, we found that cortistatin A (1) showed highly selective anti-proliferative activity against human umbilical vein endothelial cells (HUVECs). The characteristic structure and intriguing biological activity of 1 attracted synthetic chemists, and many synthetic studies have been reported. We also engaged in synthetic study of 1 for overcoming the scarcity of natural supply. Here we present a new synthetic approach toward 1 using intramolecular Heck cyclization as a key step, and synthesis of some readily accessible analogs of 1. 1. Synthetic study toward total synthesis First, an A-ring fragment 17 was synthesized in 9 steps from 2-cyclohexen- 1 -one. Coupling reaction between the A-ring fragment 17 and a CD-ring fragment 16, which was obtained in 2 steps from readily available (+)-Hajos-Parrish ketone, afforded 21 and subsequent manipulations gave an enol triflate 25. The intramolecular Heck cyclization of 25 proceeded through 7 -endo manner to give compound 26b. After conversion of 26b into an enone 13, oxy-Michael reaction furnished a carbocyclic core structure of 1. Further study toward total synthesis of 1 is now under investigating. 2. Design and synthesis of active lead compounds Although many synthetic reports of cortistatin A (1) have been appeared, there have been no report about the in vivo anti-tumor properties of cortistatins by using the synthesized compounds. Then we are engaging in synthetic study of the structurally simplified and readily available analogs of cortistatins, based on the 3-D structure of 1 and the structure-activity relationship of the isolated eleven minor cortistatins. We found that a synthesized compound 37 having isoquinoline moiety and tetracyclic planar core structure showed potent and selective anti-proliferative activity against HUVECs. The compound 37 also exhibited in vivo anti-tumor activity in a mouse model inoculated sarcoma S180 cells.

収録刊行物

詳細情報 詳細情報について

  • CRID
    1390282681056740992
  • NII論文ID
    110009986597
  • DOI
    10.24496/tennenyuki.53.0_571
  • ISSN
    24331856
  • 本文言語コード
    ja
  • データソース種別
    • JaLC
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

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