The Model Synthesis of Maoecrystal

Many distinguished synthetic groups have carried out the total synthesis toward Maoecrystal V due to the complexity of the structure and the importance of its bioactivity. The thesis mainly focuses on two aspects the first part is the stereoselective construction of the tetracychc model system and the second part is the first total synthesis of natural product Maoecrystal V. Based on the model study, the total synthesis of Maoecrystal V is accomplished in 17 steps, 1.2% yield. 

In 2009, Danishefsky s group reported the model study of Maoecrystal V (Fig. 1.21) [32]. The key reactions in their study mainly include Pd(II)-catalyzed coupling reaction [2, 3] rearrangement reaction and intramolecular Diels-Alder reaction. It worth mentioning that the three research groups mentioned above used the similar synthetic strategy to complete the synthesis of core structure model of Maoecrystal V. 

In this chapter, we completed the model study of Maoecrystal V. The synthesis route is shown briefly in Fig. 2.30. 

In model study of Maoecrystal V, the skeleton of the natural product was successfully established, and three contiguous chiral centers, C8, C9, CIO, were also built. Based on the information supplied by model research, the total synthesis of Maoecrystal V was developed. The retro-synthetic analysis is shown in Fig. 3.1. 

The total synthesis of natural product Maoecrystal V was completed by an efficient convergent strategy. In the model study of Maoecrystal V, Wessly oxidative dearomatization and IMDA reaction were considered as the key reactions to rapidly construct the tetracyclic structure of Maoecrystal V, which established the foundation for total synthesis of Maoecrystal V. Through an eight-step route with a total yield of 20 %, the model study was completed with high efficiency. 

In the total synthesis of Maoecrystal V, various synthetic strategies were tried for the construction of oxa-bridge on the basis of the model research. Evenmally, from the known compound 3.13, which is very simple, the cir-diol was successfully constructed after Pinhey arylation and selective reduction of ketone groups. Divalent rhodium was utilized to catalyze intramolecular 0-H bond insertion to construct a high-tension seven-membered ring structure. Then, Wessly oxidative dearomatization/IMDA strategy was utilized to construct the key pentacycUc structure of Maoecrystal V. After 17 steps, the total synthesis of Maoecrystal V was completed with a total yield of 1.2 %. 

After careful consideration and primary exploration, we decided to utilize tandem Wessely oxidative dearomatization/IMDA strategy to construct core structure of Maoecrystal V. Figure 1.19 shows the route of model synthesis. The main purpose of the model research is to look for efficient method to construct two continuous chiral centers in the molecule and quickly synthesize the [2.2.2] ring system on the right side of the molecule stmcture. Pb(lV) mediated coupling reaction was utilized to construct chiral quaternary carbon center on the right side, and Pb(OAc)4 was added to realize tandem oxidative dearomatization/... 

Model study constructed four rings of the pentacyclic system of natural products Maoecrystal V (Fig. 2.31) and laid the foundation for the future total synthesis work. The major progresses made in our model study are as follows ... 

We developed the synthesis strategy for a convergence model and successfully synthesized the core structure of natural product Maoecrystal V. 

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