2型糖尿病是一种慢性内分泌代谢疾病，严重威胁人类健康。蛋白酪氨酸磷酸酶1B（PTP1B）在胰岛素信号转导通路中起着重要的负调控作用。分子生物学实验证明，敲除PTP1B基因，不仅可以显著提高受试小鼠对胰岛素的敏感性，而且能够明显降低肥胖症的患病机率。因此，寻找小分子PTP1B抑制剂已成为治疗2型糖尿病的新途径。.本课题组对十余种海藻进行了系统的化学成分研究，发现来源于海洋红藻松节藻Rhodomela confervoides的溴酚类化合物BPN表现出很强的PTP1B抑制活性，IC50=0.84 μmol/L。作为海洋特有的多卤代化合物，溴酚化合物的结构新颖，尤其对治疗2型糖尿病靶点PTP1B的研究并不多见。本项目以化合物BPN为研究对象，对其进行全合成以及结构衍生物的设计、合成研究，探讨构效关系、提高化合物的生物利用度，为获得新型的PTP1B抑制剂提供候选化合物。

Protein tyrosine phosphatase 1B (PTP1B), an intracellular protein tyrosine phosphatase, has been implicated in the negative regulation of insulin and leptin signal transduction pathways among other biological functions. The PTP1B null mice showed enhanced insulin sensitivity, lower plasma glucose and insulin levels, and resistance to weight gain compared to control mice when fed high fat diets. Further biochemical validation of PTP1B as a therapeutic target for diabetes and obesity has been from a variety of sources, including antisense oligionucleotide studies, overexpression in vitro, human single nucleotide polymorphisms, and observations of mutations within the human PTP1B gene sequence.On the basis of On the basis of these data, PTP1B is currently considered one of the best validated biological targets for non-insulin dependent diabetes and obesity. .Bromophenols are widely distributed throughout the marine red algae and have been reported to exhibit a wide spectrum of biological and pharmacological activities including antibacterial, antifeedant, α-glucosidase inhibition and cytotoxic activities. BPN, a kind of bromophenol from red algae Rhodomela confervoides showed significant inhibitory activity against PTP1B (IC50=0.84 μmol/L). In the present study, we performed total synthesis of BPN in order to solve the resource of this natural product. Additionally, in an effort to improve PTP1B inhibitory activity, optimization of BPN by extension of the molecule from structure-activity relationshiop and bioavailability was explored to identi?cation of novel cell permeable, orally bioavailable, small molecule PTP1B inhibitors.