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Acta Chimica Sinica >

2012 , Vol. 70 >Issue 21: 2232 - 2235

DOI: https://doi.org/10.6023/A12090626

Article

Studies on the Total Synthesis of 8-epi-Liphagal

  • Peng Jinbao ,
  • Hou Xiaojun ,
  • Zhang Shuyu ,
  • Tu Yongqiang
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  • State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000

Received date: 2012-09-04

  Online published: 2012-10-11

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21072085, 20921120404, 21102061, 20972059, 21290180), 973 program (No. 2010CB833203), the “111” Program of MOE and the Key National S&T Program “Major New Drug Development” of Ministry of Health of China (No. 2012ZX09201101-003).

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Abstract

The tetracyclic meroterpenoid natural product (＋)-liphagal is one of a number of natural inhibitors of phosphatidylinositol 3-kinase (PI3K), which plays a central role in regulation of cell proliferation, cell survival, adhesion, membrane trafficking, glucose transport and neurite growth. Liphagal also shows inhibitory activity against PI3Kα with an IC50 of 100 nmol·L-1 making it as an agent for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. From a structural point of view, liphagal has an unprecedented [6-7-5-6] tetracyclic skeleton, and has attracted significant attention from the synthetic chemists. Starting from cheap and commercially available 2,4,5-trimethoxylbenzaldehyde and α-ionone, an advanced intermediate 10 for the synthesis of 8-epi-liphagal was achieved in the longest linear 7 steps and 8.72% yield. The key reactions include: Wittig reaction, Cu-catalyzed cyclization, chemoselective hydrogenation and Friedel-Crafts reaction.

Key words： liphagal; natural product; synthesis; Friedel-Crafts reaction; advanced intermediates

Cite this article

Peng Jinbao , Hou Xiaojun , Zhang Shuyu , Tu Yongqiang . Studies on the Total Synthesis of 8-epi-Liphagal[J]. Acta Chimica Sinica, 2012 , 70(21) : 2232 -2235 . DOI: 10.6023/A12090626

References

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