16 シグナルペプチダーゼII阻害剤グロボマイシンの構造決定と不斉全合成(口頭発表の部)

• 木方 俊宏

  三共・創薬研

• 中山 瑞香

  三共・創薬研

• 古源 寛

  三共・創薬研

• 古川 洋司

  三共・BM研

• 木下 武

  三共・BM研

• 犬飼 正俊

  三共・探索研

書誌事項

タイトル別名

• 16 Crystal Structure and Asymmetric Total Synthesis of Globomycin, a Selective Signal Peptidase II Inhibitor

抄録

Globomycin (1) was isolated as a 19-menbered cyclic depsipeptide antibiotic which consists of glycine, L-allo-isoleucine, L-allo-threonine. L-serine, N-Me-leucine, and 3-hydroxy-2-methylnonanoic acid, in 1978. 1 has been proven to be a specific inhibitor of Signal peptidase II, which processes the acylated precursor form of lipoproteins into apolipoprotein and signal peptide in Esherichia coli. 1 was used routinely to demonstrate the acylation of the newly identified lipoprotein, and since then it has been widely used to control the maturation of the lipopeptides. Although 1 has been an invaluable tool in studies of lipoprotein biosynthesis to date, its structure remains obscure for almost two decades. An initial structure elucidation of 1 only determined the absolute stereochemistry of L-allo-Thr-L-Ser-L-allo-Ile moiety. Relative stereochemistry of 3-hydroxy-2-methylnonanoic acid and absolute stereochemistry of N-Me-leucine moieties still remained ambiguous. The structure of 1 which was unequivocally determined by X-ray crystallography, revealed that the absolute stereochemistry of ambiguous moieties are (2R, 3R)-3-hydroxy-2-methylnonanoic acid and N-Me-L-leucine. The crystal structure of 1 suggested the carbonyl oxygen of the L-allo-Ile forms an intramolecular hydrogen bond to the NH of glycine. We also achieved an asymmetric total synthesis of 1 by convergent coupling of three fragments followed by macrocyclization. The physical and spectroscopic data of synthetic 1 were identical to those of natural globomycin.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 42 (0), 91-96, 2000

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681055167104
• NII論文ID: 110006681918
• DOI: 10.24496/tennenyuki.42.0_91
• 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