Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Sep 3;16(33):9944-62.
doi: 10.1002/chem.201000741.

Chemistry and biology of the caged Garcinia xanthones

Oraphin Chantarasriwong  1 , Ayse Batova, Warinthorn Chavasiri, Emmanuel A Theodorakis
Affiliations
Review

Chemistry and biology of the caged Garcinia xanthones

Oraphin Chantarasriwong et al. Chemistry. .

Abstract

Natural products have been a great source of many small molecule drugs for various diseases. In spite of recent advances in biochemical engineering and fermentation technologies that allow us to explore microorganisms and the marine environment as alternative sources of drugs, more than 70 % of the current small molecule therapeutics derive their structures from plants used in traditional medicine. Natural-product-based drug discovery relies heavily on advances made in the sciences of biology and chemistry. Whereas biology aims to investigate the mode of action of a natural product, chemistry aims to overcome challenges related to its supply, bioactivity, and target selectivity. This review summarizes the explorations of the caged Garcinia xanthones, a family of plant metabolites that possess a unique chemical structure, potent bioactivities, and a promising pharmacology for drug design and development.

PubMed Disclaimer

Figures

Figure 1
Figure 1
a) Garcinia mangostana; b) mangosteen; c) gamboge and gambogic acid; and d) an extract from a Japanese painting in which gamboge was used as the yellow colorant.
Scheme 1
Scheme 1
Proposed biosynthesis of benzophenones and xanthones in higher plants. NADP+ = Nicotinamide adenine dinucleotide phosphate.
Scheme 2
Scheme 2
Proposed biosynthesis of the caged xanthone motif through a cascade of nucleophilic attacks.
Scheme 3
Scheme 3
Proposed biosynthesis of the caged xanthone motif by a Claisen/Diels–Alder reaction cascade.
Scheme 4
Scheme 4
Representative examples of caged structures 45 and 48 formed by a Wessely oxidation/Diels–Alder reaction cascade.
Scheme 5
Scheme 5
Synthesis of caged structures 51 and 54.
Scheme 6
Scheme 6
Synthesis of caged structures 56 and 57.
Scheme 7
Scheme 7
Model studies on the Claisen/Diels–Alder reaction cascade with prenylated coumarin 59.
Scheme 8
Scheme 8
Construction of caged structures 67, 68 and 71 through a biomimetic Claisen/Diels–Alder reaction cascade. SEM = [2-(trimethylsilyl)ethoxy]methyl.
Scheme 9
Scheme 9
Biomimetic synthesis of forbesione (8) and related structures through a Claisen/Diels–Alder/Claisen reaction cascade. ND = yield not determined.
Scheme 10
Scheme 10
Solvent effect on the rate of the Claisen/Diels–Alder reaction cascade. MOM = methoxymethyl.
Scheme 11
Scheme 11
Biomimetic synthesis of 6-O-methylforbesione. TBAF = tetrabutylammonium fluoride, Bn = benzyl, TBS = tert-butyldimethylsilyl.
Scheme 12
Scheme 12
Unified biomimetic synthesis of caged Garcinia xanthones.
Scheme 13
Scheme 13
Biomimetic synthesis of gambogin (2). HMDS = hexamethyldisilazane, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene.
Scheme 14
Scheme 14
Synthetic plans toward lateriflorone (22) based on biogenetic scenarios.
Scheme 15
Scheme 15
Synthesis of chromenequinone 95. MEMCl = 2-methoxyethoxymethyl chloride, DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
Scheme 16
Scheme 16
Synthesis of secolateriflorone (104). DIPEA = N,N-diisopropylethylamine, m-CPBA = m-chloroperoxybenzoic acid, HATU = 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate.
Scheme 17
Scheme 17
Synthesis of C11-methyllateriflorone (110). EDC = N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide, DMAP = 4-(N,N-dimethylamino)pyridine, TFA = trifluoroacetate, PPTS = pyridinium p-toluenesulfonate.
Scheme 18
Scheme 18
Selected structures of gambogic acid conjugates.
Scheme 19
Scheme 19
Selected structures of gambogic acid derivatives containing functionalities at the C9–C10 bond.
Scheme 20
Scheme 20
Selected caged structures used to evaluate the minimum pharmacophore of the caged Garcinia xanthones.
Scheme 21
Scheme 21
Summary of SAR studies with 1 and related analogues.
Scheme 22
Scheme 22
Optimized synthesis of cluvenone (119) by using a Pd0-catalyzed reverse prenylation reaction.
See this image and copyright information in PMC

References

    1. Gustafsson MHG, Bittrich V, Stevens PF. Int J Plant Sci. 2002;163:1045–1054.
    2. Sultanbawa MUS. Tetrahedron. 1980;36:1465–1506.
    1. Mabberley DJ. The Plant-book: A Portable Dictionary of the Vascular Plants. 2. Cambridge University Press; New York: 1997. p. 293.
    1. Kumar P, Baslas RK. Herba Hung. 1980;19:81–91.
    1. Morton JF. In: Fruits of Warm Climates. Dowling CF Jr, editor. Florida Flair Books; Miami: 1987. pp. 301–304.
    2. Howes FN. Vegetable Gums and Resins. Waltham, Mass: 1949. p. 161.
    1. Winter J. In: Artists’ Pigments: A Handbook of their History and Characteristics. Fitzhugh EW, editor. Vol. 3. Oxford University Press; New York: 1997. pp. 143–155.

Publication types

LinkOut - more resources