利用有机合成技术，对活性天然产物进行全合成或结构修饰，成为近年研究无毒防污剂的新思路。改善脂溶性和发掘功能基团是研究此类防污剂的两个重要内容。引入长脂肪烃基，能增加化合物的脂溶性；改变功能基团的位置、类别，能改变化合物的生物活性。本课题组前期研究表明，从海洋生物中获得的2,5-二酮哌嗪衍生物具有较好的抗附着活性，经卤代芳烃修饰后，衍生物活性明显增强。本项目旨在采用有机化学和药物化学方法，结合化学生物学技术，以2,5-二酮哌嗪为基本骨架，以抗藤壶幼虫和草苔虫幼虫附着活性筛选为导向，在骨架上引入长脂肪烃基和卤代芳基，研究卤代芳烃的取代位置、类型对高脂溶性2,5-二酮哌嗪衍生物抗附着活性的影响规律，研究构效关系，发现新的先导结构；同时对多个中间体采用一锅法合成，提高产率降低生产成本，并优化目标物的合成条件，结合毒性研究，为研制一类新型高效价廉的、环境友好型抗污剂奠定基础。

Total synthesis or modification of the active marine natural products by synthetic techniques is becoming a new manner to find non-toxic antifouling compounds in recent years. The introduction of alkyl groups will increase the lipophilicity of compounds and the altering of the positions or categories of functional substituents will change the bioactivity of derivatives. A few of previous studies by our group showed that 2,5-diketopiperazine derivatives obtained from marine organisms had strong anti-adhesion activities, and their anti-adhesion ability would be highly improved by the introduction of halo-contained aromatic groups substituted on the 2,5-diketopiperazine scaffold. Cooperated with organic chemistry, medicinal chemistry and chemical biological methods or techniques, and guided by the anti-adhesion bioassay screen models, this research is focusing on the design, synthesis and anti-adhesion activity of the derivatives derived from marine natural products of cyclic-dipeptides by the introduction of side alkyl groups and halo-contained aromatic groups substituted at the 3 or 6-position of 2,5-diketopiperazine scaffold, and protected at 1-position of nitrogen atom so as to avoid the formation of intermolecular hydrogen bonds. Based on these changes, a novel series of small molecules will be synthesized and used as a new class of non-toxic anti-adhesion agents. The impacts of the positions and categories of the halo-contained aromatic groups on the anti-adhesion activity of 2,5-diketopiperazine derivatives will be studied, and the structural-activity relationships will be also investigated for find new lead compounds. The method for the synthesis of some intermediates was optimized by using one-pot reaction, and the routes and conditions for the synthesis of the target derivatives will be also optimized in favor of developing an efficient, inexpensive and green antifoulants.