P-37 ファルネシルトランスフェラーゼ阻害剤Andrastin類の合成研究(ポスター発表の部)

DOI

書誌事項

タイトル別名
  • P-37 Synthetic Studies toward Protein Farnesyltransferase Inhibitor Andrastins

抄録

Ras proteins are subjected to posttranslational farnesylation at a cysteine the fourth residue from the C-terminus, in which protein farnesyltransferase (PFTase) is concerned. Andrastins A-D are unique meroterpenoids (mixed polyketide-terpenoid) and novel protein farnesyltransferase inhibitors. Since farnesylation is essential for the transforming activity of mutated Ras proteins, andrastins are expected to be promising antitumor agents. Andrastins were found from the cultured broth of Penicillium sp. FO-3929 by Omura and co-workers in 1996. The novel tetracyclic carbon skeletons of these meroterpenoids having six or seven stereogenic centers and an angularly disubstituted perhydrobenzo[e]indene moiety, comprise the B, C and D rings. Although their unusual structures and biological activities have made them the subject of intense synthetic interest, the total synthesis of andrastins has not yet been reported probably due to their structural complexity. In this paper, we describe efficient and general methods for the syntheses of the perhydrophenanthrene (ABC ring system) and the fully functionalized perhydrobenzo[e]indene (BCD ring system) of andrastins A-D. Both sytheses commence from Wieland-Miescher ketone, and the former features intramolecular Diels-Alder raction and the latter is characterized by using a Ti(III)-mediated radical cyclization or an ene reaction. These reactions were successfully applied to the constructions of the both ring systems.

収録刊行物

詳細情報

  • CRID
    1390282681054094720
  • NII論文ID
    110006682679
  • DOI
    10.24496/tennenyuki.48.0_349
  • 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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