Total synthesis and biological activity of dolastatin 16
Total synthesis and biological activity of dolastatin 16
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DOI：
10.1039/c6ob02657e
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发表时间：
2017-02-07
影响因子：
3.2
通讯作者：
Matsuda, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Casalme, Loida O.;Yamauchi, Arisa;Matsuda, Fuyuhiko
Dolastatin 16是一种由Pettit等人首次从海兔Dolabella aurcularia中分离得到的具有潜在抗肿瘤代谢产物的大环去脂肽，其全合成是以一种收敛的方式实现的。据Tan报道，Dolastatin 16具有很强的防污活性，因此有望抑制海洋底栖生物，如两栖动物在船舶和水下人工结构物上的附着。因此，Dolastatin 16是一种潜在的化合物，可以作为一种新型的环保防污材料来取代禁用的三丁基锡防污涂料。Dolastatin 16的合成涉及到在多肽偶联过程中使用Pro来阻止由L-Pro和N-甲基-D-Valine组成的二酮基哌嗪的形成。这种延长多肽链的策略允许高效和可扩展地合成一段，随后与第二段偶联并环化形成多司他丁16的大环骨架。合成的多司他丁16具有与天然多司他丁16相似的抗污染活性，对文昌鱼的鲤鱼幼虫具有类似的抑制活性。
The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.