Prenylated caged xanthones: Chemistry and biology

Figures & data

Figure 1.  Garcinia hanburyi; a. gamboge (resin), b. fruits, c. flowers, d. tree.

Scheme 1.  Proposed biosynthetic pathway via a tandem Claisen rearrangement/intramolecular Diels-Alder reaction.

Table 1.  Natural sources of prenylated caged xanthones.

Plants	Parts	Caged xanthones
G. morella (Figure 2)	seeds	desoxymorellin (1), morellin (2), morellinol (6), dihydroisomorellin (22), moreollin (25), isomoreollin (26) (Adawadkar et al., 1976; Bhat et al., 1964; Kartha et al., 1963; Rao, 1937; Subba et al., 1978)
	resin	isomorellin (3), morellic acid (4), isomorellic acid (5) (Karanjgaonkar et al., 1966; Nair & Venkataraman, 1964)
G. hanburyi (Figure 2)	resin	desoxymorellin (1), isomorellin (3), morellic acid (4), isomorellic acid (5), isomorellinol (7), morellin dimethyl acetal (8), gambogin (9), gambogic aldehyde (10), gambogic acid (11), epigambogic acid (12), isogambogic acid (13), epiisogambogic acid (14), 30-hydroxygambogic acid (15), 30-hydroxyepigambogic acid (16), 7-methoxygambogic acid (17), 7-methoxyepigambogic acid (18), 7-methyoxydesoxymorellin (19), 7-methoxyisomorellinol (20), isomoreollin B (23), methyl 8,8a-dihydromorellate (24), moreollic acid (27), 8,8a-Dihydro-8-hydroxymorellic acid (28), 8,8a-dihydro-8-hydroxygambogic acid (29/30), gambogoic acid A or 10-methoxygambogic acid (31), gambogoic acid B or 10-ethoxygambogic acid (32), oxygambogic acid (34), gambogefic acid (36), gambogellic acid (37), 7-methoxygambogellic acid (38), desoxygaudichaudione A (40), hanburin (41), gaudichaudic acid (42), desoxygambogenin (43), gambogenin (44), isogambogenin (45), gambogenic acid (46), isogambogenic acid (47), gambogenin dimethyl acetal (48), 3-O-geranylforbesione (49), 8,8a-dihydro-8-hydroxygambogenic acid (50), 10-methoxygambogenic acid (51), gambogenific acid (52) (Asano et al., 1996; Feng et al., 2008; Han et al., 2006a, 2006b, 2006c; Lee & Chen, 2006; Lin et al., 1993; Ollis et al., 1965; Reutrakul et al., 2007; Tao et al., 2009; Wang et al., 2008a)
	fruits	desoxymorellin (1), isomorellin (3), morellic acid (4), isomorellinol (7), gambogic acid (11), 8,8a-epoxymorellic acid (21), dihydroisomorellin (22), isomoreollin B (23), moreollic acid (27), hanburinone (33), forbesione (39), 2-isoprenylforbesione (desoxyqaudichaudione A) (40), desoxygambogenin (43) (Reutrakul et al., 2007; Sukpondma et al., 2005a)
	whole plant	gambogic acid (11), neogambogic acid (35) (Lu et al., 1984)
G. forbesii (Figure 2)	branches	forbesione (39) (Leong et al., 1996)
G. gaudichaudii (Figure 3)	leaves	morellic acid (4), forbesione (39), gaudichaudiones A–H (53–60), gaudichaudiones I-J (61-62), gaudichaudiic acids A–E (63–67) (Cao et al., 1998a, 1998b; Wu et al., 2000)
	barks	gaudichaudiic acids F–I (68–71), 7-isoprenylmorellic acid (72) (Wu et al., 2001; Xu et al., 2000)
G. scortechinii (Figure 4)	twigs	scortechinones A–C (73–75) (Rukachaisirikul et al., 2000)
	latex	scortechinones A–J (73–82) (Rukachaisirikul et al., 2003)
	stem bark	scortechinones A–B, D, F, I–J, L–P (73–74, 76, 78, 81–82, 83–87) (Rukachaisirikul et al., 2005)
	fruits	scortechinones A–F, H–I, L–M, P–T (73–78, 80–81, 83–84, 87–91) (Sukpondma et al., 2005b)
G. bracteata (Figure 5)	leaves	bractatin (92), 1-O-methylbractatin (93), isobractatin (94), 1-O-methylisobractatin (95), 1-O-methyl-8-methoxy-8,8a-dihydrobractatin (96), 1-O-methylneobractatin (97) (Thoison et al., 2000)
	barks	neoisobractatin A (98), neoisobractatin B (99) (Thoison et al., 2005)
	twigs	bractatin (92), isobractatin (94), 1-O-methylisobractatin (95), neoisobractatin A (98), neoisobractatin B (99), 3-O-methylbractatin (100), neobractatin (101), 3-O-methylneobractatin (102) (Na et al., 2010a, 2010b)
G. cantleyana (Figure 6)	trunk bark	deoxygaudichaudione A (40), gaudichaudione H (60), 7-hydroxyforbesione (103), cantleyanones A-D (104–107) (Shadid et al., 2007)
G. lateriflora (Figure 6)	stem bark	(−)-morellic acid (4), (−)-isogaudichaudiic acid (108), (−)-isogaudichaudiic acid B (109), (−)-isogaudichaudiic acid E (110), (−)-isomoreollic acid (111), (−)-11,12-dihydro-12-hydroxymorellic acid (112) (Ren et al., 2010)
G. urophylla (Figure 6)	leaves	gaudichaudione H (60), 7-hydroxydesoxymorellin (113) (Khalid et al., 2007)
D. sootepense (Figure 5)	leaves	isobractatin or sootepenseone (94) (Reutrakul et al., 2001)
C. cochinchinense (Figure 6)	roots	cochinchinoxanthone (114), cochinchinones C-D (115–116) (Mahabusarakam et al., 2006)
	stems	cochinchinoxanthone (114) (Ren et al., 2011b)

Figure 2.  Prenylated caged xanthones from G. hanburyi, G. morella, and G. forbesii.

Figure 3.  Prenylated caged xanthones from G. gaudichaudii.

Figure 4.  Prenylated caged xanthones from G. scortechinii.

Figure 5.  Prenylated caged xanthones from G. bracteata.

Figure 6.  Prenylated caged xanthones from G. cantleyana, G. lateriflora, G. urophylla, and Cratoxylum cochinchinense.

Figure 7.  Absolute configuration of the caged structure of compounds 4, 11, and 114.

Adawadkar PD, Srinivasan R, Yemul SS. (1976). Coloring matters of Garcinia morella: Part VIII. Morellinol, dihydromorelloflavone and morelloflavone-7”-β-glucoside. Indian J Chem Sect B, 17, 19–21.

 Google Scholar

Bhat HB, Nair PM, Venkataraman K. (1964). The colouring matters of Garcinia morella. Part V. Isolation of desoxymorellin and dihydroisomorellin. Ind J Chem, 2, 405–409.

 Google Scholar

Kartha G, Ramachandran GN, Bhat HB, Nair PM, Raghavan VKV, Venkataraman K. (1963). The constitution of morellin. Tetrahedron Lett, 4, 459–472.

 Google Scholar

Rao BS. (1937). Morellin, a constituent of the seeds of Garcinia morella. J Chem Soc, 853–855.

 Google Scholar

Subba Rao GSR, Rathnamala S, Sivaramakrishnan R. (1978). Structure of moreollin, a pigment isolated from Garcinia morella Desser. Proc Indian Acad Sci, 87, 75–86.

 Google Scholar

Karanjgaonkar CG, Madhavan Nair P, Venkataraman K. (1966). Morellic, isomorellic and gambogic acids. Tetrahedron Lett, 7, 687–691.

 Google Scholar

Nair PM, Venkataraman K. (1964). The colouring matters of Garcinia morella. Part IV. Isomorellin. Ind J Chem, 2, 402–404.

 Google Scholar

Asano J, Chiba K, Tada M, Yoshii T. (1996). Cytotoxic xanthones from Garcinia hanburyi. Phytochemistry, 41, 815–820.

 PubMed Web of Science ®Google Scholar

Han QB, Wang YL, Yang L, Tso TF, Qiao CF, Song JZ, Xu LJ, Chen SL, Yang DJ, Xu HX. (2006a). Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi. Chem Pharm Bull, 54, 265–267.

 PubMed Web of Science ®Google Scholar

Han Q, Yang L, Liu Y, Wang Y, Qiao C, Song J, Xu L, Yang D, Chen S, Xu H. (2006b). Gambogic acid and epigambogic acid, C-2 epimers with novel anticancer effects from Garcinia hanburyi. Planta Med, 72, 281–284.

 PubMed Web of Science ®Google Scholar

Han QB, Yang L, Wang YL, Qiao CF, Song JZ, Sun HD, Xu HX. (2006c). A pair of novel cytotoxic polyprenylated xanthone epimers from gamboges. Chem Biodivers, 3, 101–105.

 PubMed Web of Science ®Google Scholar

Lee SB, Chen CM. (2006). Compounds isolated from gamboges resin having activity in inhibiting the growth of tumor/cancer cells and pharmaceutical compositions comprising the same. US Pat Appl Publ, 22 p.

 Google Scholar

Lin L, Lin L, Pezzuto JM, Cordell GA. (1993). Isogambogic acid and isomorellinol from Garcinia hanburyi. Mag Reson Chem, 31, 340–347.

 Web of Science ®Google Scholar

Ollis WD, Ramsay MVJ, Sutherland IO, Mongkolsuk S. (1965). The constitution of gambogic acid. Tetrahedron, 21, 1453–1470.

 Web of Science ®Google Scholar

Reutrakul V, Anantachoke N, Pohmakotr M, Jaipetch T, Sophasan S, Yoosook C, Kasisit J, Napaswat C, Santisuk T, Tuchinda P. (2007). Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi. Planta Med, 73, 33–40.

 PubMed Web of Science ®Google Scholar

Tao SJ, Guan SH, Wang W, Lu ZQ, Chen GT, Sha N, Yue QX, Liu X, Guo DA. (2009). Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi. J Nat Prod, 72, 117–124.

 PubMed Web of Science ®Google Scholar

Wang LL, Li ZL, Xu YP, Liu XQ, Pei YH, Jing YK, Hua HM. (2008a). A new cytotoxic caged polyprenylated xanthone from the resin of Garcinia hanburyi. Chin Chem Lett, 19, 1221–1223.

 Web of Science ®Google Scholar

Sukpondma Y, Rukachaisirikul V, Phongpaichit S. (2005a). Antibacterial caged-tetraprenylated xanthones from the fruits of Garcinia hanburyi. Chem Pharm Bull, 53, 850–852.

 PubMed Web of Science ®Google Scholar

Lu GB, Yang XX, Huang QS. (1984). Isolation and structure of neo-gambogic acid from Gamboge (Garcinia hanburryi). Yao Xue Xue Bao, 19, 636–639.

 PubMedGoogle Scholar

Leong Y, Harrison LJ, Bannett GJ, Tan HTW. (1996). Forbesione, a modified xanthone from Garcinia forbesii. J Chem Res, 392–393.

 Web of Science ®Google Scholar

Cao SG, Wu XH, Sim KY, Tan BHK, Pereira JT, Wong WH, Hew NF, Goh SH. (1998a). Cytotoxic caged tetraprenylated xanthonoids from Garcinia gaudichaudii (Guttiferae). Tetrahedron Lett, 39, 3353–3356.

 Web of Science ®Google Scholar

Cao SG, Sng VHL, Wu XH, Sim KY, Tan BHK, Pereira JT, Goh SH. (1998b). Novel cytotoxic polyprenylated xanthonoids from Garcinia gaudichaudii (Guttiferae). Tetrahedron, 54, 10915–10924.

 Web of Science ®Google Scholar

Wu XH, Tan BKH, Cao SG, Sim KY, Goh SH. (2000). Two minor, cytotoxic caged xanthonoids from Garcinia gaudichaudii. Nat Prod Lett, 453–458.

 Google Scholar

Wu J, Xu YJ, Cheng XF, Harrison LJ, Sim KY, Goh SH. (2001). A highly rearranged tetraprenyl xanthonoid from Garcinia gaudichaudii (Guttiferae). Tetrahedron Lett, 42, 727–729.

 Web of Science ®Google Scholar

Xu YJ, Yip SC, Kosela S, Fitri E, Hana M, Goh SH, Sim KY. (2000). Novel cytotoxic, polyprenylated heptacyclic xanthonoids from Indonesian Garcinia gaudichaudii (Guttiferae). Org Lett, 2, 3945–3948.

 PubMed Web of Science ®Google Scholar

Rukachaisirikul V, Kaewnok W, Koysomboon S, Phongpaichit S, Taylor WC. (2000). Caged-tetraprenylated xanthones from Garcinia scortechinii. Tetrahedron, 56, 8539–8543.

 Web of Science ®Google Scholar

Rukachaisirikul V, Painuphong P, Sukpondma Y, Koysomboon S, Sawangchote P, Taylor WC. (2003). Caged-triprenylated and -tetraprenylated xanthones from the latex of Garcinia scortechinii. J Nat Prod, 66, 933–938.

 PubMed Web of Science ®Google Scholar

Rukachaisirikul V, Phainuphong P, Sukpondma Y, Phongpaichit S, Taylor WC. (2005). Antibacterial caged-tetraprenylated xanthones from the stem bark of Garcinia scortechinii. Planta Med, 71, 165–170.

 PubMed Web of Science ®Google Scholar

Sukpondma Y, Rukachaisirikul V, Phongpaichit S. (2005b). Xanthone and sesquiterpene derivatives from the fruits of Garcinia scortechinii. J Nat Prod, 68, 1010–1017.

 PubMed Web of Science ®Google Scholar

Thoison O, Fahy J, Dumontet V, Chiaroni A, Riche C, Tri MV, Sévenet T. (2000). Cytotoxic prenylxanthones from Garcinia bracteata. J Nat Prod, 63, 441–446.

 PubMed Web of Science ®Google Scholar

Thoison O, Cuong DD, Gramain A, Chiaroni A, Hung NV, Sevenet T. (2005). Further rearranged prenylxanthones and benzoquinones from Garcinia bracteata. Tetrahedron, 61, 8529–8535.

 Web of Science ®Google Scholar

Na Z, Hu HB, Fan QF. (2010a). A novel caged-prenylxanthone from Garcinia bracteata. Chin Chem Lett, 21, 443–445.

 Web of Science ®Google Scholar

Na Z, Hu HB, Fan QF. (2010b). Three new caged prenylxanthones from Garcinia bracteata. Helv Chim Acta, 93, 958–963.

 Web of Science ®Google Scholar

Shadid KA, Shaari K, Abas F, Israf DA, Hamzah AS, Syakroni N, Saha K, Lajis NH. (2007). Cytotoxic caged-polyprenylated xanthonoids and a xanthone from Garcinia cantleyana. Phytochemistry, 68, 2537–2544.

 PubMed Web of Science ®Google Scholar

Ren Y, Lantvit DD, Carcache de Blanco EJ, Kardono LB, Riswan S, Chai H, Cottrell CE, Farnsworth NR, Swanson SM, Ding Y, Li XC, Marais JP, Ferreira D, Kinghorn AD. (2010). Proteasome-inhibitory and cytotoxic constituents of Garcinia lateriflora: Absolute configuration of caged xanthones. Tetrahedron, 66, 5311–5320.

 PubMed Web of Science ®Google Scholar

Khalid RM, Jabit ML, Abas F, Stanslas J, Shaari K, Lajis NH. (2007). Cytotoxic xanthones from the leaves of Garcinia urophylla. Nat Prod Commun, 2, 271–6.

 Web of Science ®Google Scholar

Reutrakul V, Santisuk T, Noessner G, Schmidt J, Nickel B, Klenner T, Hose S. (2001). Novel xanthone compounds, their preparation and use medicament. Eur Pat Appl, EP 1065210 A1, 17 pp.

 Google Scholar

Mahabusarakam W, Nuangnaowarat W, Taylor WC. (2006). Xanthone derivatives from Cratoxylum cochinchinense roots. Phytochemistry, 67, 470–474.

 PubMed Web of Science ®Google Scholar

Ren Y, Matthew S, Lantvit DD, Ninh TN, Chai H, Fuchs JR, Soejarto DD, de Blanco EJ, Swanson SM, Kinghorn AD. (2011b). Cytotoxic and NF-κB inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues. J Nat Prod, 74, 1117–1125.

 PubMed Web of Science ®Google Scholar