The First Total Synthesis Of(±)-δ-Rubromycin,(+)-Coriandrone A And B&Studies On The Total Synthesis Of Vigatolide B

This thesis aims at the studies on the total synthesis of natural products (±)-δ-rubromycin,(+)-coriandrone A&B and vigatolide B, and the contents could be divided into the following three parts:Chapter1First total synthesis of natural product (±)-δ-rubromycinThe isolation, structural characterization, biological activities and total synthesis of rubromycins were introduced comprehensively. The first total synthesis of (±)-δ-rubromycin has been achieved through a convergent strategy with a longest linear sequence of11steps from known compound1-115in a6.8%overall yield. The key points of our synthetic strategy including:Sonogashira coupling reaction was used to link the two key building blocks (isocoumarin fragment and naphthalene portion); Palladium, gold and silver reagents were screened in the spiroketalization of different precursors; A new method for the synthesis of isocoumarin fragment was explored; A Danishefsky-type Diels-Alder reaction was employed to install the requisite highly functionalized aromatic ring system of the naphthalene portion, in a very short sequence, which makes the total synthesis of this natural product more efficient and elegant. This synthesis avoids the "Electron Withdrawing Resonance&Inductive Effects" and provides a new idea for the construction of spiroketals, as well as an efficient and convergent approach to synthesizing rubromycins. Chapter2First total asymmetric synthesis of natural products (+)-coriandrone A and BThe isolation, structural characterization, and biological activities of (+)-coriandrone A&B were introduced briefly. The first asymmetric total synthesis of (+)-coriandrone A and B was accomplished through a divergent synthesis in10and11steps from commercially available methyl2-hydroxy-4-methoxybenzoate, respectively. The synthesis afforded (+)-coriandrone A and B with good enantioselectivity in26.3%and21.6%overall yield. Key reactions included a Claison rearrangement, a Shi epoxidation-cyclisation sequence, and a reaction involving ortho-metallation of t-butylbenzamide with (S)-(-)-propylene oxide. This synthesis may also be useful as a model for similar natural products with benzopyran, dihydrobenzofuran, or isocoumarin fragments. Chapter3Studies on the synthesis of natural product virgatolide BThe isolation, structural characterization, and biological activities of virgatolides were introduced briefly. Studies towards the total synthesis of virgatolide B were carried out. In the model reaction, the construction of A, C, D ring skeleton have been completed successfully, and the5-membered lactone3-21and the spiroketal compound3-32were obtained; In the process of total synthesis of virgatolide B, the key intermediate aldehyde3-28was prepared from3,5-dihydroxybenzoic acid. The successful preparation of compounds3-21,3-32and3-48has laid a solid foundation for the total synthesis of virgatolides B and A. Related work is still in progress.