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天然环酯肽Hikiamides A-C的全合成

傅东林, 饶雪敏, 徐进宜, 谢唯佳, 吴晓明

傅东林, 饶雪敏, 徐进宜, 谢唯佳, 吴晓明. 天然环酯肽Hikiamides A-C的全合成[J]. 中国药科大学学报, 2018, 49(2): 181-186. DOI: 10.11665/j.issn.1000-5048.20180207
引用本文: 傅东林, 饶雪敏, 徐进宜, 谢唯佳, 吴晓明. 天然环酯肽Hikiamides A-C的全合成[J]. 中国药科大学学报, 2018, 49(2): 181-186. DOI: 10.11665/j.issn.1000-5048.20180207
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FU Donglin, RAO Xuemin, XU Jinyi, XIE Weijia, WU Xiaoming. Total synthesis of cyclodepsipeptide Hikiamides A-C[J]. Journal of China Pharmaceutical University, 2018, 49(2): 181-186. DOI: 10.11665/j.issn.1000-5048.20180207
Citation: FU Donglin, RAO Xuemin, XU Jinyi, XIE Weijia, WU Xiaoming. Total synthesis of cyclodepsipeptide Hikiamides A-C[J]. Journal of China Pharmaceutical University, 2018, 49(2): 181-186. DOI: 10.11665/j.issn.1000-5048.20180207
shu

天然环酯肽Hikiamides A-C的全合成

  • 1.

    中国药科大学药物科学研究院

  • 2.

    中国药科大学药物化学教研室

Total synthesis of cyclodepsipeptide Hikiamides A-C

摘要

    摘要
  • 摘要: 设计完成了环酯肽类活性天然产物Hikiamides A - C 的全合成:以市售氮端或羧基端保护的氨基酸为原料，采用片段汇聚式的液相缩合方法。首先，分别制备三肽片段(化合物 5a / 5b )和二肽片段(化合物 8a / 8b )；然后，经过缩合、催化氢化得到直链五肽(化合物 9a / 9b / 9c )；最后，在混合缩合剂(PyBOP和HBTU)的作用下，关环得到Hikiamides A - C ，总收率分别为9%、11%和6.5%。该液相全合成方法具有经济性强、操作简便，收率高等优点，有效解决了Hikiamides A - C 天然来源获得性较差的问题。
    Abstract: Total synthesis of cyclodepsipeptide Hikiamides A - C was described. Fragment convergent condensation method was applied for the preparation of Hikiamides A - C , starting from Commercially available amino acid such as L-N-Boc-Phe-OH, L-N-Boc-Trp-OH, L-N-Cbz-Van-OH etc. Tripeptide fragments(compounds 5a / 5b )and dipeptide fragments(compounds 8a / 8b )were first prepared. The subsequent condensation of the resulted two fragments provided protected linear pentapetides(compounds 9a / 9b / 9c ); Finally, the linear pentapetide was cyclized by a mixed condensing agents comprised of PyBOP and HBTU. Hikiamides A - C was obtained with total yields of 9%, 11% and 6. 5%, respectively. Compared with the natural source, this method has the advantages of low cost, convenient operation and high yield, which effectively solves the problem of low isolated yield of Hikiamides A - C from Fusarium sp.
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    • 参考文献(17)
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  • 刊出日期:  2018-04-24

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