Total Synthesis of Maoecrystal

An intramolecular conjugate addition strategy was explored that successfully formed the targeted C—O bond but resulted in the undesired stereochemistry for the total synthesis of maoecrystal V (13TL635). An asymmetric oxa-Michael/Michael cascade reaction of Jt-quinols and a,(3-unsaturated aldehydes provided access to four contiguous stereocenters of the hindered tetrahydrofuran with good diastereoselection (13CS2828). 

Gong J, Lin G, Li C-C et al. (2009) Synthetic study toward the total synthesis of maoecrystal V. Org Lett 11 4770-4773 (Reprinted with permission. Copyright (2010) American Chemical Society.)... 

This thesis focuses on the total synthesis of Maoecrystal V. Maoecrystal V, a natural product with potent biological activity, is a novel diterpenoid which was isolated from the leaves of Chinese medicinal herb, Isodon eriocalyx, by Prof. Handong Sun and co-workers. The synthesis challenge exists in the novel pentacyclic ring system and six chiral centers, including four continuous chiral centers, three all quaternary carbon centers. 

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. 

J. Gong, Total Synthesis of ( )-Maoecrystal V, Springer Theses,... 

Though the strategy developed by Trauner s group has some unique features in the construction of the core structure of the molecule, it is still difficult to realize the total synthesis of Maoecrystal V starting from intermediate 1.7.98, because ring system of the left side of the molecule has a relatively high tension (Fig. 1.29). 

At the same time, with its unique antitumor activity, Maoecrystal V draws the attention of synthetic chemists worldwide as well as brings the fierce competition in synthesis research. On the road leading to the successful total synthesis of Maoecrystal V, we are greatiy challenged. 

Peng F, Danishefsky SJ (2011) Toward the total synthesis of Maoecrystal V an intramolecular Diels—Alder route to the Maoecrystal V pentacyclic core with the appropriate relative stereochemistry. Tetrahedron Lett 52 2104—2106... 

Baitinger 1, Mayer P, Trauner D (2010) Toward the total synthesis of Maoecrystal V establishment of contiguous quaternary stereocenters. Org Lett 12 5656-5659... 

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. 

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