30(S)-hydroxybullatacin

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Total synthesis of 30(S)-hydroxybullatacin

In 2003, Marshall’s group disclosed a modular synthetic approach to the adjacent bis-THF rings (Scheme 46) [108]. This approach featured highly selective additions of chiral R-oxygenated allylic stannane and indium reagents such as B¹ and D¹ (M = SnBu₃ or InBr₂) to an acylic core aldehyde precursor (A¹ then C¹) followed by core ring closure (E¹ → F¹) and ensuing Sonogashira coupling (F¹ + G¹ → H¹) to append the butenolide segment. This straightforward strategy permitted the efficient assembly of the acetogenin structure from four basic subunits. By interchanging these subunits a variety of natural acetogenins and their isomers should be accessible in relatively few steps. They extended the scope of their modular four-component synthesis of annonaceous acetogenins to 30(S)-hydroxybullatacin (335). The ¹H and ¹³C NMR spectra of the tetraol product 335 were in complete agreement with the reported spectra [109].

Reference 109

109.	Gu, Z.-M.; Zeng, L.; Schwedler, J. T.; Wood, K. V.; McLaughlin, J. L. Phytochemistry 1995, 40, 467–477. doi:10.1016/0031-9422(95)00308-T

Go to reference 109

A synthesis of the bistetrahydrofuran Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin A through application of a previously disclosed four-component modular approach is described in which extended core segments are coupled to a C4- or C5-hydroxy butenolide terminus. The butenolide termini segments were prepared from (S)- or (R)-malic acid. Spectral properties of synthetic 30(S)-hydroxybullatacin and uvarigrandin A, as well as their Mosher ester derivatives, were in close agreement to the reported values for the natural substances. The synthetic 5(R)-uvarigrandin A is possibly identical to narumicin I, but subtle differences in the reported NMR spectra prevented an unambiguous assessment of this point.

 http://pubs.acs.org/doi/abs/10.1021/jo0266137?journalCode=joceah


 nmr seehttp://pubs.acs.org/doi/suppl/10.1021/jo0266137/suppl_file/jo0266137_s.pdf

Recent progress on the total synthesis of acetogenins from Annonaceae

Nianguang Li¹, Zhihao Shi², Yuping Tang³, Jianwei Chen¹ and Xiang Li¹

¹Department of Medicinal Chemistry, Nanjing University of Chinese Medicine, No. 138, Xianlindadao, Nanjing, Jiangsu 210046, P. R. China. Tel & Fax: +86-25-85811512
²Division of Organic Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 211198, P. R. China
³Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P. R. China.

Corresponding author email     

Beilstein J. Org. Chem. 2008, 4, No. 48.

 http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-4-48

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