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Bullatacin
the Annonaceous acetogenins
Jinyu Han, Kevin Yu, Hua Wang
(School of chemical engineering and technology, Tianjin University, Tianjin, 300072,P.R.China)
bullatacin, an adjacent bis-THF Annonaceous acetogenin, is expected to be a new candidate for anticancer agent based on the promising antitumor effect shown by in vitro as well as in vivo studies. For this reason, it is deemed essential to provide an update review about the research on bullatacin. So, in this paper, many characteristics, including chemical structure, bioactivities, isolation & purification and mechanism of bioactivities have been reviewed.
Introduction
Over the past decade, Annonaceous acetogenins have aroused many interests among botanists and chemists because of their wide range of noteworthy biological activities and their special stereostructure. Since the pioneering discovery of Uvarian by Jolad et al. [1] in 1982, the research on them has undergone a rapid development. So far, more than 250 Annonaceous acetogenins have been described from this plant family, many of which offered excellent potential for development as new antitumor, antiprotozal, antimicrobial, immunosuppressive and pesticidal agents.
However, according to the data of National Cancer Institute (NCI), bullatacin, among all the acetogenins, showed the most potent anticancer bioactivity, especially for some cancer. These data have provided the impetus for more intensive research on bullatacin. So, much research, including chemical stereostructure, biological activity, isolation & purification and mechanism of biological action has been conducted.
Source
Up to now, the sources of bullatacin can be gained in two ways: natural extraction and chemical synthesis. In the tide of “Back to Nature”, the method of natural extraction is especially preferable to other methods. What’s more, compared with other methods, the expense and the difficulty of production is relative low.
Natural extraction
Many species in the genera of Annona, family of Annonaceae, contain this valuable acetogenin—bullatacin, which especially abounds in the species of Annona bullata Rich. and Annona squamosa.
Annona bullata Rich. is a tall tree, which is indigenous to Cuba and Annona squamosa, is a deciduous arbor native to America. Bullatacin can be isolated from the extracts of seed, root and bark. Generally speaking, the content of bullatacin in the part of balk is often higher than in other parts. But in view of nature protection and sustainable development, it is not advisable to extract it from bark and should be encouraged to extract bullatacin in other parts, such as seed.
In China, from the crude abstracts of bark and seed from Annona atemoyacin, Chen W.S. [2] et al. also isolated this valuable acetogenin and reported that the content in this plant is about in the magnitude of 10-5.
Chemical synthesis
By far, Bullatacin has been successfully synthesized by chemists, such as Thomas R. Hoye[3]. However, compared with natural extraction, the method of chemical synthesis possessed many disadvantages, such as complicated procedure, high production cost, low yield due to complex structure and unique stereostructure. So, the method of chemical synthesis is still limited in the field of academia and without industrial application value.
Chemical structure
The molecular weight (MW) of bullatacin was determined on the basis of ESI — MS .The data were listed as followed: ESI—MS: 646[M+Na+H]+, 699 [M+2Na +H]+, 1270[2M+2Na+3H]+; so, its MW was 622.
CIMS (isobutane) m/z 623 (MH+), CIMS (ammonia) m/z 622 (M+NH4+–H2O), 640 (M+ NH4+), EIMS m/z 622 (M+); Hr CIMS 623.4847 (calc. 623.4889), these data showed that its molecular formula was C37H66O7. [4]
Structure of α, β-unsaturated, γ-lactone
A positive response to Kedde's reagent, the strong IR absorption at 1750 cm-1and the UV absorption maximum at 215.5 nm (ε=7974) in EtOH revealed the presence of an α,β-unsaturated, γ-lactone. The data (Table1) of HNMRδ7.19 (H-35), 5.06 (H-36), 3.85 (H-4), 2.52 (H-3a), 2.40 (H-3b), 1.44 (H-37) and CNMRδ 151.69 (C-35), 77.91 (C-36), 69.97 (C-4), 33.32 (C-3), 19.10 (C-37) both indicated that bullatacin possessed the structure of α,β-unsaturated, γ-lactone and a hydroxyl group at the position of C-4.
Table1 NMR data of γ-lactone type of bullatacin[5]
Type 1 2 3a 3b 4 35 36 37
δH — — 2.52 (ddt) 2.40 (dd) 3.85 7.19 5.06 (dda) 1.44
δC 174.60 131.28 33.32 33.32 69.97 151.69 77.91 19.10
Note: δH: CDCl3, 600MHZ; δC: CDCl3, 150MHZ
So, α, β-unsaturated, γ-lactone subunit of bullatacin can be listed as followed [6] (fig.1)
Fig.1 Structure of α, β-unsaturated, γ-lactone
Structure of bis-tetrahydrofuran ring
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作者:admin@医学,生命科学 2011-03-06 17:22
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