天然产物作为药物发现的源泉，在现代医药研发中占据着重要地位。目前已发现的天然产物绝大多数是以单体形式存在的。然而，一些天然产物可以通过二聚化反应得到结构更为复杂的二聚体，并且表现出与单体不同的结构和生物活性多样性。而二聚体天然产物在自然界中相对含量少，仅依靠分离得到的样品无法对其生物功能进行系统深入的研究。此外，大多数二聚体类天然产物结构非常复杂，具有相当的合成挑战性。本论文围绕两类具有复杂结构和潜在药用价值的二聚体天然产物展开全合成研究，并取得了丰富的研究成果。在论文的第一部分工作中，我们实现了苍耳烷倍半萜二聚体Pungiolides以及相关同源化合物的全合成。苍耳烷型倍半萜是从传统中药苍耳中发现的一大类具有结构和生物活性多样性的天然产物。迄今为止，自然界中已发现的该类天然产物超过100个，并表现出多种生理活性，被视为发现新药或先导化合物的重要物质基础。苍耳烷二聚体高度复杂的骨架结构及多样的生物活性，引起了我们的研究兴趣。我们发展了一条高效简洁的不对称合成路线，以手性磷酸催化的串联allyboration/lactonization反应为关键步骤，仅通过7步反应即实现了苍耳烷单体8-epi-xanthatin的全合成。在此基础上，通过仿生串联反应完成复杂天然产物Xanthipungolide的首次全合成。另外，同样以该化合物为前体，以仿生Diels-Alder二聚化反应为关键步骤，实现了Pungiolide A, B, D, E和L–N等多个苍耳烷型倍半萜二聚体的首次全合成。论文第二部分主要工作是实现了二聚体天然产物Homodimericin A的全合成。Homodimericin A是从真菌T. harzianum和细菌Streptomyces sp.共生条件下产生的次级代谢产物中分离发现的一种天然产物，具有复杂的笼状骨架和多个连续手性中心。尽管关于Homodimericin如何抵抗细菌侵袭的具体作用机制尚不明确，但此类化合物的发现为发展新型抗菌药物提供了良好的起点。该天然产物复杂新颖的分子结构和有趣的氧化应激作用机制引起了我们的合成兴趣。基于对分子结构和生源来源的理解，我们认为多取代苯醌化合物为其生源合成前体，从而设计了仿生二聚化的合成。从三个简单易得的原料出发, 利用Moore重排反应、两次Michael加成反应以及仿生串联Diels-Alder/carbonyl ene反应为关键步骤,实现了 Homodimericin A 的高效全合成。 综上所述，本论文完成了包括Pungiolides和Homodimericin A在内的两类二聚体天然产物的首次全合成。在研究工作中，我们秉承理性设计和生源

As a rich source for the discovery of drugs or leading compounds, natural products play an exemely important role in the areas of pharmaceutical industry and chemical pesticides. Structurally, while most of natural products exist in monomeric forms, some could undergo dimerization to form the corresponding dimeric compunds which display unusual structural and biological diversity. Of note, most of the dimeric natural products have low abundance in nature, which larely restrict their widespread application in biomedical study. Meanwhile, most of the dimeric natural products feature beautiful yet daunting molecular architectures, which pose considerable challenging targets for synthetic chemists. In this thesis, we successfully complete the total synthese of two groups of dimeric natural products which bear complex structures and promising biological profiles. The major achievements are summarized as follows.In the first part of this thesis, we successfully achieved the total syntheses of a series of dimeric xanthanolides including pungiolides A, B, D, E, and L-N, as well as some related congeners. Xanthanolides represent a large family of natural products which display diverse biological profiles and complex structures. So far, over one hundred members have been elucidated in xanthanolides family, most of which are characterized by a 5/7 bicyclic framework. Comparably, a small group of xanthanolides dimers, namely pungiolides, have been discovered over the past several years, which largely enrich the checmial and biological diversity of xanthanolides. Attracted by the fascinating structures of the dimeic xanthanolides, as well as their intriguing biological activities, we embarked on a synthetic program directed towards their total syntheses. For this end, the enantioselective synthesis of (+)-8-epi-xanthatin, a key xanthanolide monomer, was achieved from readily available starting materials in seven longest linear steps, hinging on a chiral phosphoric acid-catalyzed tandem allylboration/lactonization reaction. With (+)-8-epi-xanthatin as precursor, the total synthesis of xanthipungolide, one of the most complicated xanthanolide monomers, was accessed through a bio-inspired tandem double bond isomerization/6π electronic cyclization/intramolecular Diels-Alder reaction. Moreover, a group of xanthanolide dimers including pungiolides A, B, D, E, and L-N were assembled through a bio-inspired Diels-Alder dimerization followed by late-stage diversificationIn the second part of the thesis, we successfully completed the total synthesis of dimeric natural product homodimericin A. Homodimericin A is a fungal metabolite, which possesses an unprecedented and highly complex hexacyclic framework. It also plays a crucial role in the fungus’s chemical defense to exogenous oxidative stress. The unique molecular architectures and the intriguing biological mechanism of the antioxidative stress stimulated considerable research interest from us. We have realized a total synthesis of homodimericin A based on a series of rationally designed and bio-inspired transformations, the key elements of which include a Moore rearrangement to assemble its monomeric hydroquinone precursor, a homo-dimerization via double Michael additions to construct its planar A/B/C tricyclic framework, and a tandem Diels-Alder reaction/carbonyl ene-cyclization to forge its congested D/E/F tricyclic cage motif. In addition, unequivocal evidence for the structural elucidation of homodimericin A is also provided.In summary, we have completed the total syntheses of two groups of complex dimeric natural products including pungiolides and homodimericin A. The success of our syntheses hinges on a series of rationally designed and bio-inspired reactions. In both cases, the biomimetic homo-dimerization reactions are employed as key steps to construct the polycyclic core of the targets, followed by the carefully implemented late-stage functionalizations to access the natural products. Our work not only helps to get deep insight into the underlying biosynthetic origins of the chased targets, but also paves the way to systematically explore their biological function and medical use.