天然环酯肽Hikiamides A-C的全合成

Total synthesis of cyclodepsipeptide Hikiamides A-C

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(Py BOP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。

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.