ACETOGENINS AND STYRYLLACTONES

Hilwan Yuda Teruna, PhD Sekolah Tinggi Ilmu Farmasi Riau Plants have been utilised for many purposes by humans since before recorded history. One of the important uses is as a source of medicinal agents. and Cox, 1996). The first written records of the use of plants for Since then, human beings have never stopped medicinal purposes dates back to about 2600 BC in Mesopotamia (Balick depending on plants for their health. The major sources of plant medicines are from tropical forests. Of about 250,000 higher plant species, more than half are found in the tropical rain forests (Soejarto, 1993). Approximately 20,000 plant species have been recorded as traditional medicines (Soejarto, 1993) and some 600 botanical items have been recognized in various editions of The United States Pharmacopoeia (Tyler, 1993). Styryl-lactones are important constituents primitive families, such as in a number of The first Equisetaceae, Lauraceae, Piperaceae,

Ranunculaceae and Zingeberaceae (Blazquez et al., 1999).

styryl-lactone found in the Annonaceae was goniothalamin, isolated from Goniothalamus andersonii, G. macrophyllus and G. malayanus (Jewers et al., 1972). This compound had previously been reported from Cryptocarya caloneura (Lauraceae) (Hlubucek and Robertson, 1967). In one review, Blazquez (1999) found that Goniothalamus appeared to be a major producer of styryl-lactones. Figure 1.5 illustrates six types of styryl-lactones.

O O O O O O O

Styryl-pyrone

Fura no-pyrone

Fura no-furone
O

O O O O O

Pyra no-pyra ne

Bute nolide

Heptolide

Figure 1.5: Types of styryl-lactones. In 1982 Jolad et al. (1982) reported uvaricin (33) the first of a new group of compounds from the Annonaceae that were believed to be polyketide derivatives (later they became known as the annonaceous acetogenin class of compounds). Stereochemistry, absolute or relative, of the compound was not established at that time (Figure 1.6). compound demonstrated potent antitumor activities.
OAc O O O O OH H

This

3 3 . Uva ricin

Figure 1.6: The first annonaceous acetogenin. The finding of this acetogenin triggered an extensive search for more of these compounds in annonaceous plants. Numerous acetogenins have now been isolated with a wide range of biological effects including pesticidal, fungicidal, antimalarial, antiprotozoal and antimicrobial activities. Moreover, it appears that annonaceous acetogenins are distributed in only a limited number of genera within the Annonaceae (Alali et al., 1999a).

Until 1997, 39 species from 9 different genera had been reported to contain acetogenins, Annona (15 species), Asimina (4 species), Disepalum (1 species), Goniothalamus (4 species), Polyalthia (1 species), Porcelia (1 species), Rollina (7 species), Uvaria (5 species) and Xylopia (1 species) (Zafra-Polo et al., 1998). Recently, five more species from Goniothalamus, G. cheliensis (Li et al., 1997b; Li et al., 1998), G. dolichocarpus (Goh et al., 1995b), G. gardneri (Chen et al., 1997; Chen et al., 1998b; Seidel et al., 1999), G. leiocarpus (Mu et al., 1998) and G. velutinus (Ee, 1998) have been demonstrated to contain acetogenins. Acetogenins At least twenty-eight species have been studied and their constituents are listed in Table 1.2. These phytochemical studies have revealed the importance of this genus as a source of styryl-lactones and acetogenins, with other classes of compounds such as isoquinoline alkaloids also being significant (Blazquez et al., 1999; Cave et al., 1997; Waterman, 1993; Zafra-Polo et al., 1996). Isolation of acetogenins from plant materials is usually started with extraction with ethanol or methanol. The alcoholic extracts then are subjected to a series of liquid/liquid partitions with increasing polarity. Each fraction is monitored by TLC and bioassays such as the brine shrimp lethality test (BST). Kedde's reagent is used to detect acetogenins on the TLC plates. Positive fractions are then subjected to fractionation processes by silica gel columns, circular partition or preparative HPLC. Many acetogenins exist as epimeric pairs that cannot be easily separated, although semi-preparative HPLC can sometimes be successful. Reversed-phase C18 HPLC column gives better result than normal-phase silica gel (Alali et al., 1999a; Cave et al., 1997). Countercurrent chromatography has been employed to concentrate acetogenin fractions. However, further purification with

HPLC is still necessary (Alali et al., 1999a). 3

Since 1997, liquid chromatography-electrospray ionization mass spectroscopy (LC/EIMS) has been introduced to detect acetogenins. The pattern of fragmentation is reproducible, using the positive-ion mode and under conditions of dissociation atmospheric (APICID). pressure This technique in-source collision-induced

produces the spectra that show [M+Na]+ and [M+H]+, as well as the loss of water molecules [H2O] several times (Gu et al., 1997).

Table 1.2: Distribution of constituents in the genus Goniothalamus Species

G. amuyon G. andersonii G. arvensis G. borneensis

Type of Constituents
Acetogenins, alkaloids and styryl-lactones Alkaloids and styryllactones Styryl-lactones Alkaloids, a flavonoid, a phenylpropane, a phytosterol and styryllactones A phytosterol and styryllactones Acetogenins, a flavonoidalkaloid and styryllactones An acetogenin and styryllactones Acetogenins A flavonoid A styryl-lactone Acetogenins Acetogenins and styryllactones

References
(Lu et al., 1985; Wu et al., 1991; Wu et al., 1992) (Ee et al., 1998; Jewers et al., 1972; Tanaka et al., 1997) (Bermejo et al., 1995; Bermejo et al., 1998a; Bermejo et al., 1998b) (Cao et al., 1998)

G. cardiopetalus G. cheliensis G. dolichocarpus G. donnaiensis G. fasciculatus G. fulvus G. gardneri G. giganteus

(Hisham et al., 2000; Hisham et al., 2003) (Gu et al., 2000; Li et al., 1997b; Li et al., 1998; Wang et al., 2002) (Goh et al., 1995a; Goh et al., 1995b) (Jiang et al., 1997; Jiang and Yu, 1997a; Jiang and Yu, 1997b; Jiang et al., 1998a; Jiang et al., 1998b; Jiang et al., 1998c) (Zakaria et al., 2000) (Zakaria et al., 1989) (Chen et al., 1997; Chen et al., 1998b; Chen et al., 1998c; Seidel et al., 1999) (Alali et al., 1997a; Alali et al., 1997b; Alali et al., 1998b; Alali et al., 1999b; Alkofahi et al., 1988; Alkofahi et al., 1990; Fang et al., 1991a; Fang et al., 1991b; Fang et al., 1992a; Fang et al., 1992b; Fang et al., 1993; Gu et al., 1994a; Zeng et al., 1996a; Zeng et al., 1996b; Zhang et al., 1995) (Khan et al., 1998; Khan et al., 1999) (Alali et al., 1999b; Chen et al., 1998a; Hu et al., 1999a; Hu et al., 1999b; Li et al., 1997a; Mu et al., 2003a; Talapatra et al., 1985a; Talapatra et al., 1985b; Zhang et al., 1993; Zhang et al., 1999a; Zhang et al., 1999b) (Chen et al., 1998a; Zhang et al., 1993) (Mu et al., 1996; Mu et al., 1998; Mu et al., 1999a; Mu et al., 1999b; Mu et al., 2003b) (Jewers et al., 1972; Sam et al., 1987)

G. grandiflorus G. griffithii

Styryl-lactones Alkaloids, a cyclopeptide, a triterpene, phytosterols and styryl-lactones

G. howii G. leiocarpus G. macrophyllus

Acetogenins, a styryllactone and a phenylpropanoid Acetogenins, cyclopeptides and styryllactone Styryl-lactones

Table 1.2 (Cont.): Distribution of constituents in the genus Goniothalamus Species

G. malayanus G. marcanii G. montanus G. ridleyi G. scortechinii G. sesquipedalis G. tapis G. thwaitesii G. umbrosus G. uvarioides G. velutinus

Type of Constituents
Essential oils and styryllactones Alkaloids and a quinone A styryl-lactone Sesquiterpenes, styryllactones Alkaloids and a styryllactone An acetogenin, alkaloids, a peptide, phytosterols and styryl-lactones Alkaloids, sesquiterpenes, phytosterols and styryllactones Flavonoids and triterpenes Styryl-lactones Styryl-lactones Alkaloids and styryllactones

References
(Colegate et al., 1990; Inayat-Hussain et al., 2002; Jantan and Ahmad, 2002; Jewers et al., 1972) (Soonthornchareonnon et al., 1999) (Colegate et al., 1990) (Ee et al., 1999) (Din et al., 1990; Zakaria et al., 1989) (Hasan et al., 1994; Hasan et al., 1995; Hasan et al., 1996; Mia et al., 1997; Talapatra et al., 1985b; Talapatra et al., 1988) (Colegate et al., 1990; Ee et al., 2000; Zakaria et al., 1989) (Seidel et al., 2000) (Ahmad and Din, 2002) (Ahmad et al., 1991) (Ee, 1998)

Structure elucidation of acetogenins is not an easy task. compounds. Mosher

Early

investigations could not establish the absolute stereochemistry of the This was because of the complex stereochemistry and However, the application of the to determine the relative Positions of method has helped waxy nature of these compounds. ester

stereochemistry of some oxygen bearing carbons.

tetrahydofuran (THF) and hydroxyl groups can be predicted by analysing the fragmentation pattern of EI-MS, CI-MS or FAB-MS. Moreover synthetic models have helped phytochemists to predict the relative stereochemistry of the THF ring systems, with their flanking hydroxyls and of the 4-hydroxyled- -lactone ring (Alali et al., 1999a). So far, only gigantecin, a non-adjacent bis-THF acetogenin has yielded to Xray analysis (Yu et al., 1994). In his review McLaughlin (1999) observed that more than 350 annonaceous acetogenins had been reported (Alali et al., 1999a). To 6

date approximately 400 acetogenins have been isolated. Goniothalamus (Table 1.3).

Of the 46-

acetogenins bearing species known in the Annonaceae nine belong to Types of acetogenins found in Goniothalamus have been grouped based on the number of tetrahydofuran (THF) rings, mono-THF, bis-THF, non-adjacent bis-THF, tri-THF or pyran rings, or the absence of rings (linear) in the molecules and sub grouped by the form of the -lactone ring (unsaturated -methyl--lactone, a propanone substituted

unsaturated -lactone or a -hydroxy--methyl--lactone) (Cave et al., 1997). Figures 1.7, 1.8, 1.9, 1.10, 1.11 and 1.12 show the mono-THF, bis-THF, nonadjacent bis-THF, pyran and non-THF acetogenins, respectively. Acetogenins have a wide range of biological activities. Extensive studies revealed that they have cytotoxic, antitumor, antiparasitic, pesticidal, antimicrobial, antifungal and immunosuppressive properties (Alali et al., 1999a; Cave et al., 1997). The structures of acetogenins are very crucial in terms of their activities. For example, annonacin (42) has a cytotoxic activity against KB cells ED 50 1 x 10-4 g/mL, whilst its ketone derivative, annonacinone showed only 1 x 10-3 g/mL (Cave et al., 1997). Their cytotoxic mechanism is as inhibitors of mitochondrial complex I (Alali et al., 1999a). Annonacin (42), howiicin B (70) and howiicin C (46) exhibit a filaricidal activity against Molidema dessetae (Cave et al., 1997). Annomontacin (41) and gigantetrocin A demonstrate a pesticidal activity against some cockroach panels (Alali et al., 1999a). Many acetogenins, especially of those with unsaturated -hydroxyl--methyl-lactone rings, have not been tested for their biological activities. Table 1.3: Acetogenins from the genus Goniothalamus Species and Compounds Type of Acetogenins References

Goniothalamus amuyon Annonacin (42) Corossolin (46) Gigantriocin (62) Goniothalamus cheliensis Cheliensisin B (43) Cheliensisin C (44) Goniothalamus dolichocarpus Annonacin (42) Goniothalamus donnaiensis Annonacin (42) Isoannonacin (71) Donbutocin (91) Donhepocin (92) 34-epi-Donhepocin Donhexocin (93) Donnaienin (47) Donnaienin A (48) 34-epi-Donnaienin A Donnaienin B (49) 34-epi-Donnaienin B Donnaienin C (50) 34-epi-Donnaienin C Donnaienin D (94) 34-epi-Donnaienin D

Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF

(Li and Chang, 1996) (Li and Chang, 1996) (Li and Chang, 1996) (Li et al., 1997b) (Li et al., 1997b)

Mono-THF Mono-THF Mono-THF Linear Linear Linear Linear Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Linear Linear

(Goh et al., 1995b) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Jiang et al., 1998c) (Jiang et al., 1998c) (Jiang et al., 1998c) (Jiang and Yu, 1997b) (Jiang et al., 1998c) (Jiang et al., 1998b) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Jiang et al., 1998a) (Jiang et al., 1998a) (Jiang et al., 1998a) (Jiang et al., 1998a)

Table 1.3 (cont.): Acetogenins from the genus Goniothalamus Species and Compounds
2,4-cis-Gigantetrocinone (76) 2,4 transGigantetrocinone Goniodonin (65) Goniothalamicin (68) Murisolin (70) Goniothalamus gardneri Annonacin (42) Isoannonacin (71) Gardnerilin A (95) Gardnerilin B (96)

Type of Acetogenins
Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Linear Linear

References
(Jiang et al., 1997) (Jiang et al., 1997) (Jiang et al., 1997) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Chen (Chen (Chen (Chen et et et et al., al., al., al., 1997) 1997) 1998c) 1998c)

Gardnerin (51) Gardnerinin (52) 34-epi-Gardnerinin Gigantetrocin A (54) Gigantetrocin B (55) Goniothalamicin (68) Goniothalamusin (97) Goniothalamus giganteus Annomontacin (41) 4-Deoxyannomontacin (45) cis- Annomontacinone (75) trans-Annomontacinone Annonacin (42) 2,4-cis-Isoannonacin (78) 2,4-trans-Isoannonacin Asimilobin (80) Giganenin (53) Giganin (90) Gigantecin (84) 4-Deoxygigantecin (85) 2,4-cis-Gigantecinone (86) 2,4-trans-Gigantecinone Gigantetrocin (54) 4-Acetylgigantetrocin A (54) 2,4-cis-Gigantetrocinone (76) 2,4-transGigantetrocinone Gigantetronenin (57) Gigantransenin A (59) Gigantransenin B (60) Gigantransenin C (61) Gigantriocin (62) Gigantrionenin (63) cis-Gigantrionenin (64) Goniocin (87) Goniodenin (81) Gonionenin (66) 2,4-cis-Gonioneninone (77) 2,4-trans-Gonioneninone Goniotetracin (67)

Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Linear Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Adjacent bis-THF Mono-THF Linear Non Adjacent bis-THF Non Adjacent bis-THF Non Adjacent bis-THF Non Adjacent bis-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF tri-THF Adjacent bis-THF Mono-THF Mono-THF Mono-THF Mono-THF

(Chen et al., 1997) (Chen et al., 1998b) (Chen et al., 1998b) (Chen et al., 1997) (Chen et al., 1997) (Chen et al., 1997) (Seidel et al., 1999) (Fang et al., 1992a) (Alali et al., 1997b) (Alali et al., 1997b) (Alali et al., 1997b) (Alkofahi et al., 1988) (Alali et al., 1997a) (Alali et al., 1997a) (Zhang et al., 1995) (Fang et al., 1992b) (Fang et al., 1993) (Alkofahi et al., 1990) (Fang et al., 1992b) (Alali et al., 1997a) (Alali et al., 1997a) (Alali et al., 1997a) (Fang et al., 1991b) (Zeng et al., 1996b) (Alali et al., 1997b) (Alali et al., 1997b) (Fang et al., 1992a) (Zeng et al., 1996a) (Zeng et al., 1996a) (Zeng et al., 1996a) (Fang et al., 1991b) (Fang et al., 1991b) (Fang et al., 1992a) (Zeng et al., 1996b) (Gu et al., 1994a) (Zhang et al., 1995) (Gu et al., 1994b) (Alali et al., 1998b) (Alali et al., 1998b) (Alali et al., 1998b) (Alali et al., 1998b)

Table 1.3 (cont.): Acetogenins from the genus Goniothalamus Species and Compounds
Goniothalamicin (68) Goniotriocin (83) Goniotrionin (69)

Type of Acetogenins
Mono-THF Non Adjacent bis-THF Mono-THF

References
(Alkofahi et al., 1988) (Alali et al., 1998b) (Alali et al., 1999b) (Alali et al., 1998a)

Longicoricin (72) Longifolicin (73) Longimicin C (82) Pyragonicin (88) Pyranicin (89) Xylomaticin (74) 2,4-cis-Xylomaticinone (79) 2,4-transXylomaticinone Goniothalamus howii Howiicin A (42) Howiicin B (70) Howiicin C (46) Howiinin D (62) Howiicin E (71) Howiicin F (54) Howicin G (55) Goniothalamus leiocarpus Annonacin (42) Corossoline (46) Gigantriocin (62) Murisolin (70) Goniothalamus sesquipedalis Gigantetrocin (54) Goniothalamus velutinus Annonacin (42)

Mono-THF Mono-THF Adjacent bis-THF Pyran Pyran Mono-THF Mono-THF Mono-THF

(Alali (Alali (Alali (Alali (Alali (Alali (Alali

et et et et et et et

al., al., al., al., al., al., al.,

1997b) 1997b) 1997a) 1998a) 1998a) 1997b) 1999b)

(Alali et al., 1999b)

Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF Mono-THF

(Zhang et al., 1993) (Zhang et al., 1993) (Zhang et al., 1993) (Chen et al., 1998a) (Yang et al., 1994) (Yang et al., 1994) (Zhang et al., 1993) (Mu (Mu (Mu (Mu et et et et al., al., al., al., 1998) 1998) 1998) 1998)

Mono-THF Mono-THF

(Hasan et al., 1996) (Ee, 1998)

10

OH O (CH2)n

R3

(CH2)n R2

O O R1

Compound Names
41 Annomontacin 42 Annonacin =howiicin A

No. of Carbo ns
37 35

Furan ring and Position

er/trans/er at 17 er/trans/er at 15

R1
H H

R2
OH OH

R3
OH OH

Others and Position

OH at 10 OH at 10

Sourc es
GGI GAM GDO GDN GGA GGI GHO GLE GVE GCH

Reference
(Fang et al., 1992a) (Li and Chang, 1996) (Goh et al., 1995b) (Jiang and Yu, 1997a) (Chen et al., 1997) (Alkofahi et al., 1988) (Zhang et al., 1993) (Mu et al., 1998) (Ee, 1998) (Li et al., 1997b)

OH at 10 & 11, stereochemistry not stated 44 Cheliensisin C 35 At 15 H OH OH OH at 10, GCH (Li et al., 1997b) stereochemistry not stated Note: er=erythro and th=threo; db=double bond; GAM=G. amuyon, GCH=G. cheliensis, GDO= G. dolichocarpus, GDN=G. donnaiensis, GGA=G. gardneri, GGI=G. giganteus, GHO=G. howii, GLE=G. leiocarpus, GSE=G. sesquipedalis, GVE=G. velutinus

43 Cheliensisin B

35

At 15

OH

OH

11

Figure 1.7: Mono-THF acetogenins of Goniothalamus.

OH O (CH2)n

R3

(CH2)n R2

O O R1

Compound Name
45 4-deoxyannomontacin A 46 4-deoxyannonacin =corossolin =howiicin C 47 Donnaienin 48 Donnaienin A and 34-epi-donnaienin A 49 Donnaienin B and 34-epi-donnaienin B 50 Donnaienin C and 34-epi-donnaienin C

No. of Carbo ns
37 35 35 35 35 37

Furan ring and Position

er/trans/er at 17 th/trans/th at 15 er/trans/er at 13 er/trans/er at 15 trans/er at 9 er/trans/er at 15

R1
H H H OH H OH

R2
H H OH OH OH OAc

R3
OH OH OH OH H OH

Others and Position

OH at 10 OH at 10 OH at 10 & 15 mixture OH at 17 & 18 (er),mixture OH at 10, mixture

Sourc es
GGI GAM GHO GLE GDN GDN GDN GDN GDN GDN

Reference
(Alali et al., 1997b) (Li and Chang, 1996) (Zhang et al., 1993) (Mu et al., 1998) (Jiang et al., 1998b) (Jiang and Yu, 1997a) (Jiang and Yu, 1997a) (Jiang et al., 1998a)

12

51 Gardnerin 52 Gardnerinin and

35 35

OH at 10, 19 & 20 34-epi-gardnerinin (er), mixture 53 Giganenin 37 th/trans/th at H H OH OH at 10 and db 13 at 21-22 Note: er=erythro and th=threo; db=double bond; GAM=G. amuyon, GCH=G. cheliensis, donnaiensis, GGA=G. gardneri, GGI=G. giganteus, GHO=G. howii, GLE=G. leiocarpus, GSE=G. sesquipedalis, GVE=G. velutinus

er/trans/er at 15 trans/er at 11

H OH

OH OH

OH H

OH at 8 & 10

GGA GGA GGA GGI

(Chen et al., 1997) (Chen et al., 1998b) (Fang et al., 1992b)

GDO= G. dolichocarpus, GDN=G.

Figure 1.7 (cont.): Mono-THF acetogenins of Goniothalamus.

13

OH O (CH2)n

R3

(CH2)n R2

O O R1

Compound Name
54 Gigantetrocin =gigantetrocin A =densicomacin-2 =howiicin F 55 Gigantetrocin B =howiicin G 56 4acetylgigantetrocin A 57 Gigantetronenin 58 Gigantetronin 59 Gigantransenin A 60 Gigantransenin B

No. of Carbo ns
35

Furan ring and Position

trans/th at 9

R1
H

R2
OH

R3
H

Others and Position

OH at 17 & 18 (th) OH at 17 & 18 (th) isomer of gigantetrocin OH at 17 & 18 (th) OH at 17 & 18 (th) cis db at 2122 OH at 17 & 18 (th) OH at 23 and trans db at 21-22 OH at 23 and trans db at 21-22 (23 epimer of Gigantransenin A

Sourc es
GGA GGI GHO GSE GGA GHO GGI GGI GGI GGI GGI

Reference
(Chen et al., 1997) (Fang et al., 1991b) (Yang et al., 1994) (Hasan et al., 1996) (Chen et al., 1997) (Zhang et al., 1993) (Zeng et al., 1996b) (Fang et al., 1992a) (Fang et al., 1992a) (Zeng et al., 1996a) (Zeng et al., 1996a)

35 37 37 37 37 37

trans/th at 9 trans/th at 9 trans/er at 9 trans/th at 9 er/trans/er at 13 er/trans/er at 13

H H H H H H

OH OAc OH OH H H

H H H H OH OH

14

Note: er=erythro and th=threo; db=double bond; GAM=G. amuyon, GCH=G. cheliensis, GDO= G. dolichocarpus, GDN=G. donnaiensis, GGA=G. gardneri, GGI=G. giganteus, GHO=G. howii, GLE=G. leiocarpus, GSE=G. sesquipedalis, GVE=G. velutinus

Figure 1.7 (cont.): Mono-THF acetogenins of Goniothalamus.

OH O (CH2)n

R3

(CH2)n R2

O O R1

Compound Name
61 Gigantransenin C 62 Gigantriocin =howiicin D 63 Gigantrionenin 64 cis-gigantrionenin 65 Goniodonin 66 Gonionenin

No. of Carbo ns
37 35

Furan ring and Position

er/trans/er at 13 trans/th at 9

R1
H H

R2
H H

R3
OH H

Others and Position

OH at 21 and trans db at 22-23 OH at 17 & 18 (th) OH at 17 & 18 (th) OH at 17 & 18 (th) OH at 10 cis, db at 21-22

Sourc es
GGI GAM GGI GHO GLE GGI GGI GDN GGI

Reference
(Zeng et al., 1996a) (Li and Chang, 1996) (Fang et al., 1991b) (Zhang et al., 1993) (Mu et al., 1998) (Fang et al., 1992a) (Zeng et al., 1996b) (Jiang et al., 1997) (Gu et al., 1994b)

37 37 35 37

trans/th at 9 cis/th at 9 er/trans/er at 13 th/trans/th at

H H OH H

H H OH OH

H H OH OH

15

67 Goniotetracin 68 Goniothalamicin

37 35

(Jiang and Yu, 1997a) (Chen et al., 1997) (Alkofahi et al., 1988) (Alali et al., 1998b) GHO (Zhang et al., 1994) Note: er=erythro and th=threo; db=double bond; GAM=G. amuyon, GCH=G. cheliensis, GDO= G. dolichocarpus, GDN=G. donnaiensis, GGA=G. gardneri, GGI=G. giganteus, GHO=G. howii, GLE=G. leiocarpus, GSE=G. sesquipedalis, GVE=G. velutinus

13 th/trans/th at 13 th/trans/th at 13

H H

OH OH

OH OH

OH at 10 -

GGI GDN GGA GGI

(Alali et al., 1998b) (Alali et al., 1998b)

Figure 1.7 (cont.): Mono-THF acetogenins of Goniothalamus.

OH O (CH2)n R3 O O R1

(CH2)n R2

Compound Name
69 Goniotrionin 70 Howiicin B =murisolin 71 Howiicin E =muricatetrocin A

No. of Carbo ns
35 35

Furan ring and Position

th/trans/th at 9 th/trans/th at 15 At 11

R1
H H

R2
OH OH

R3
H H

Others and Position

OH at 16, cis db at 17-18 -

Sourc es
GGI GDN GHO GLE GHO

Reference
(Alali et al., 1998a) (Jiang and Yu, 1997a) (Zhang et al., 1994) (Mu et al., 1998) (Yang et al., 1994)

35

OH

Stereochemistry is not stated

16

er/trans/er at H H OH OH at 10 15 73 Longifolicin 35 th/trans/th at H H OH 13 74 Xylomaticin 37 th/trans/th at H OH OH OH at 10 13 Note: er=erythro and th=threo; db=double bond; GAM=G. amuyon, GCH=G. cheliensis, donnaiensis, GGA=G. gardneri, GGI=G. giganteus, GHO=G. howii, GLE=G. leiocarpus, GSE=G. sesquipedalis, GVE=G. velutinus

72 Longicoricin

37

GGI GGI GGI

(Alali et al., 1997b) (Alali et al., 1997b) (Alali et al., 1997b)

GDO= G. dolichocarpus, GDN=G.

Figure 1.7 (cont.): Mono-THF acetogenins of Goniothalamus.

17

OH O (CH2)n

R (CH2)m
4 2

O
1

Compound Name
75 Annomontacinone 76 Gigantetrocinone 77 Gonioneninone 78 Isoannonacin

No. of Carbons
37; m=11; n=12 35; m=3; n=16 37; m=7; n=14 35; m=9; n=10

Position of Furan ring

At 17 At 9 At 13 At 15

R
OH H

Others and Position

OH at 10; mixture of 2,4 cis and trans OH at 17 and 18 (th) mixture of 2,4 cis and trans OH at 10; cis db at 21-22; mixture of 2,4 cis and trans OH at 10; mixture of 2,4 cis and trans

Source s
GGI GDN GGI GGI GDN GGA GGI

Reference
(Alali et al., 1997b) (Jiang et al., 1997) (Alali et al., 1997b) (Alali et al., 1998b) (Jiang and Yu, 1997a) (Chen et al., 1997) (Alali et al., 1997a) (Alali et al., 1999b)

OH

79 Xylomaticinone

37; m=9; At 15 OH OH at 10; mixture of 2,4 cis GGI n=12 and trans Note: er=erythro and th=threo; db=double bond; GDN=G. donnaiensis, GGA=G. gardneri, GGI=G. giganteus,

Figure 1.7 (cont.): Mono-THF acetogenins of Goniothalamus.

18

OH O (CH2)n O

R
9

(CH2)3 OH

O O

Compound Name
80 Asimilobin 81 Goniodenin 82 Longimicin C

No. of Carbons
35; n=12 37; n=14 35; n=12

R
H H OH

Others and Position

cis double bond at 2122 -

Sources
G. giganteus G. giganteus G. giganteus

Reference
(Zhang et al., 1995) (Zhang et al., 1995) (Alali et al., 1997a)

Figure 1.8: Bis-THF acetogenins of Goniothalamus.

OH O (CH2)10 O OH O (CH2)4
9

O O

OH

Compound Name

No. of Carbons

Sources

Reference 19

83 Goniotriocin

37

G. giganteus

(Alali et al., 1999b)

Figure 1.9: Non-adjacent bis-THF acetogenin of Goniothalamus.

OH O (CH2)10 O OH
9

OH (CH2)4 R

O O

Compound Name
84 Gigantecin 85 4-deoxygigantecin

No. of Carbon s
37 37

R Sources
OH H G. giganteus G. giganteus

Reference
(Alkofahi et al., 1990) (Fang et al., 1992b) (Alali et al., 1997a)

OH O (CH2)10

OH O OH (CH2)4
9 4 2

O O

Compound Name

No. of

Others and

Sources

Reference 20

Carbon s
86 2,4-cis-gigantecinone and 2,4-trans-gigantecinone 37

Position
Mixture of cis and trans G. giganteus (Alali et al., 1999b)

Figure 1.9 (cont.): Non-adjacent bis-THF acetogenins of Goniothalamus.

21

OH (CH2)8 O O O (CH2)3 OH

O O

Compound Name
87 Goniocin

No. of Carbons
37

Sources
G. giganteus

Reference
(Gu et al., 1994a)

Figure 1.10: Tri-THF acetogenin of Goniothalamus.

OH O (CH2)12 HO
13

O (CH2)3 R2 R1 OH O

Compound Name
88 Pyragonicin 89 Pyranicin

No. of Carbons
37 37

R1
H OH

R2
OH H

Source
G. giganteus G.

Reference
(Alali et al., 1998a) (Alali et al., 1998a)

22

giganteus

Figure 1.11: Pyran acetogenins of Goniothalamus.

R7 (CH2)n R8
19

R5
15 8 4

O O R1

R6

R4

R3

R2

Compound Name
90 Giganin 91 Donbutocin 92 Donhepocin and 34-epidonhepocin 93 Donhexocin 94 Donnaienin D and 34-epidonnaienin D 95 Gardnerilin A

No. of Carbo ns
35; n=11 35; n=11 35; n=11 35; n=11 37; n=13 35; n=11

R1
H H OH

R2
H OH OH

R3
H H H

R4
OH OH OH

R5
H OH OH

R6
H OH OH

R7
H H OH

R8
H H OH

Others and Position

OH at 17 & 18 (er), cis db at 13-14 15 & 16 th 15 & 16 er; 19 and 20 th

Sourc es
GGI GDN GDN

Reference
(Fang et al., 1992a; Fang et al., 1993) (Jiang et al., 1998c) (Jiang et al., 1998c)

H OH

OH OAc

H H

OH OH

OH OH

OH OH

OH OH

OH OH

15 & 16 th; 19 & 20 th 15 & 16 er; 19 and 20 er

GDN GDN

(Jiang and Yu, 1997b) (Jiang et al., 1998a)

OH

OH

OH

OH

OH

OH

15 & 16 er; 19 and 20 er

GGA

(Chen et al., 1998c)

23

96 Gardnerilin B

35; H OH H OH H H H H OH at 17 & GGA (Chen et al., 1998c) n=11 18 (th) Note: er=erythro and th=threo; db=double bond; GDN=G. donnaiensis, GGA=G. gardneri, GGI=G. giganteus

Figure 1.12: Linear acetogenins of Goniothalamus.

24

O O

CH2OH

Compound Name
97 Goniothalamusin

No. of Carbons
25

Source
Goniothalamus gardneri

Reference
(Seidel et al., 1999)

Figure 1.12 (cont.): Linear acetogenin of Goniothalamus.

25

26

Styryl-lactones Styryl-lactones are equally important constituents found in Goniothalamus. Only five species out of 28 species that have been studied do not contain styryl-lactones. Their classification is based on their structure characteristics (Figure 1.5 on page 9). Kedde's reagent, anisaldehyl-sulphuric acid and phosphomolibdic acid are all used to detect the compounds on TLC plates. 1D and 2D NMR experiments are used to elucidate their structures, along with other spectroscopic methods such as MS, UV and IR. Unlike acetogenins, X-ray crystallography has been widely used in determining the absolute stereochemistry (Blazquez et al., 1999). These compounds possess a wide range of biological activities such as cytotoxicity, antimicrobial (goniothalamin 98) (Zhang et al., 1999b), pesticidal (isoaltholactone 119) (Ee et al., 2000) and embryotoxic (goniothalamin oxide 102) (Sam et al., 1987). Isolated styryl-lactones known from Goniothalamus, based on their sources, are listed in Table 1.4. The chemical structures of those compounds are shown in Figures 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19 and 1.20 respectively, based on their skeletal types. Table 1.4: Styryl-lactones from the genus Goniothalamus Species and Compounds
Goniothalamus amuyon 7-Acetylgoniodiol (108) 8-Acetylgoniodiol (109) 8-Chlorogoniodiol (116) 5-Deoxygoniopypyrone (132) 7,8-diepimer-Goniotriol (114) Goniotriol (111) Goniothalamin (98) Goniothalamin oxide (102) 8-Methoxygoniodiol (115) Goniothalamus andersonii 5-Deoxyisogoniopypyrone

Type

References

Styryl-pyrone Styryl-pyrone Styryl-pyrone Pyrano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Pyrano-pyrone

(Wu et al., 1991) (Lan et al., 2003) (Wu et al., 1992) (Lan et al., 2003) (Lan et al., 2003) (Lan et al., 2003) (Lan et al., 2003) (Wu et al., 1992) (Lan et al., 2003) (Lan et al., 2003) (Lan et al., 2003) (Lan et al., 2003) (Ee et al., 1998)

27

Species and Compounds

(133) Goniodiol (106)

Type
Styryl-pyrone Styryl-pyrone Styryl-pyrone Furano-pyrone Styryl-pyrone

References
(Tanaka et al., 1997) (Ee et al., 1998) (Tanaka et al., 1997) (Ee et al., 1998) (Peris et al., 2000) (Peris et al., 2000)

Goniothalamin (98) Goniothalamin oxide (102) Goniothalamus arvensis 3-Acetylaltholactone (122) 5-Acetoxyisogoniothalamin oxide (103)

Table 1.4 (cont.): Styryl-lactones from the genus Goniothalamus Species and Compounds
Almuheptolide A (141) Almuheptolide B (142) Altholactone (119) 2-epi-Altholactone (121) Arvensin (126) Etharvendiol (113) Etharvensin (125) Garvensintriol (118) Goniofufurone (128) Goniotharvensin (124) Isoaltholactone (120) Goniothalamus borneensis Goniobutenolide A (136) Goniobutenolide B (137) Goniofufurone (128) Goniothalamin (98) Goniothalenol (119) Goniotriol (111) Goniothalamus cardiopetalus Altholactone (119) Cardiopetalolactone (127) Goniopypyrone (131) Cardiobutanolide (138) Goniothalamin (98) Goniodiol (106) Goniofufurone (128) Goniofupyrone (123) Goniothalamus cheliensis Cheliensisin A (104) Goniothalamin (98) Goniothalamus clemensii 5-Acetoxygoniothalamin (99) Dehydrogoniothalamin (101)

Type
Heptolide Heptolide Furano-pyrone Furano-pyrone Furano-pyrone Styryl-pyrone Furano-pyrone Styryl-pyrone Furano-furone Furano-pyrone Furano-pyrone Butenolide Butenolide Furano-furone Styryl-pyrone Furano-pyrone Styryl-pyrone Furano-pyrone Furano-pyrone Pyrano-pyrone Butenolide Styryl-pyrone Styryl-pyrone Furano-furone Furano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone

References
(Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo (Bermejo et et et et et et et et et et et al., al., al., al., al., al., al., al., al., al., al., 1998b) 1998b) 1995) 1999) 1999) 1998a) 1997) 1998a) 1998a) 1995) 1995)

(Cao et al., 1998) (Cao et al., 1998) (Cao et al., 1998) (Cao et al., 1998) (Cao et al., 1998) (Cao et al., 1998) (Hisham (Hisham (Hisham (Hisham (Hisham (Hisham (Hisham (Hisham et et et et et et et et al., al., al., al., al., al., al., al., 2000) 2000) 2000) 2003) 2003) 2003) 2003) 2003)

(Li et al., 1998) (Li et al., 1997b) (Ahmad and Din, 2001) (Ahmad and Din, 2001)

28

Species and Compounds

Type
Styryl-pyrone Pyrano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone

References
(Ahmad and Din, 2001) (Goh (Goh (Goh (Goh (Goh et et et et et al., al., al., al., al., 1995b) 1995b) 1995b) 1995b) 1995a)

Goniothalamin (98) Goniothalamus dolichocarpus 5-Deoxyisogoniopypyrone (133) Goniodiol (106) Goniothalamin oxide (102) Goniothalamin (98) 5--Hydroxygoniothalamin (100) Goniothalamus fulvus Goniothalamin (98) Goniothalamus giganteus 8-Acetylgoniotriol (112) Altholactone (119) Goniobutenolide A (136) Goniobutenolide B (137)

Styryl-pyrone Styryl-pyrone Furano-pyrone Butenolide Butenolide

(Zakaria et al., 1989) (Fang et al., 1990) (El-Zayat et al., 1985) (Fang et al., 1991a) (Fang et al., 1991a)

Table 1.4 (cont.): Styryl-lactones from the genus Goniothalamus Species and Compounds
Goniodiol (106) Goniofufurone (128) 8-epi-Goniofufurone (129) Goniofupyrone (123) Gonioheptolide A (139) Gonioheptolide B (140) Goniopypyrone (131) 5-Deoxygoniopypyrone (132) Goniothalamin (98) Goniotriol (111) Goniothalamus grandiflorus Isoaltholactone (120) Goniothalamus griffithii 8-Acetylgoniotriol (112) 8-Acetylgoniofufurone (130) 7-Acetylgoniopypyrone (135) 7-Acetylgoniodiol (108) Altholactone (119) 5-Deoxygoniopypyrone (132) Goniodiol (106) Goniodiol diacetate (110) Goniothalamin (98) Goniotharvensin (124) Goniofufurone (128) Goniopypyrone (131) Goniotriol (111)

Type
Styryl-pyrone Furano-furone Furano-furone Furano-pyrone Heptolide Heptolide Pyrano-pyrone Pyrano-pyrone Styryl-pyrone Styryl-pyrone Furano-pyrone Styryl-pyrone Furano-furone Pyrano-pyrone Styryl-pyrone Furano-pyrone Pyrano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Furano-pyrone Furano-furone Pyrano-pyrone Styryl-pyrone

References
(Fang et al., 1991b) (Fang et al., 1990) (Fang et al., 1991b) (Fang et al., 1991a) (Fang et al., 1993) (Fang et al., 1993) (Fang et al., 1990) (Fang et al., 1991b) (El-Zayat et al., 1985) (Alkofahi et al., 1989) (Khan et al., 1998) (Chen and Yu, 1999) (Zhang et al., 1999b) (Zhang et al., 1999b) (Zhang et al., 1999b) (Chen and Yu, 1999) (Chen and Yu, 1999) (Talapatra et al., 1985) (Talapatra et al., 1985) (Chen and Yu, 1999) (Chen and Yu, 1999) (Chen and Yu, 1999) (Zhang et al., 1999b) (Zhang et al., 1999b)

29

Species and Compounds

Goniodiol (106) Goniofufurone (128) 8-epi-Goniofufurone (129) Isoaltholactone (120) Goniothalamus howii Goniothalamin (98) Howiinin A (105) Goniothalamus leiocarpus 7-epi-Goniodiol (107) Goniothalamin (98) Leiocarpin A (134) Leiocarpin B (143) Leiocarpin C (117) Leiocarpin E (144) Goniothalamus macrophyllus 0 Goniothalamin (98) Goniothalamin oxide (102) Goniothalamus malayanus Isoaltholactone (120) Goniothalamus montanus Isoaltholactone (120) Goniothalamus ridleyi Goniothalamin (98) Goniothalamin oxide (102)

Type
Styryl-pyrone Furano-furone Furano-furone Furano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Pyrano-pyrone Styryl-pyrone

References
(Fang et al., 1991b) (Fang et al., 1990) (Fang et al., 1991b) (Zhang et al., 1999b) (Zhang et al., 1993) (Chen et al., 1998) (Mu (Mu (Mu (Mu (Mu (Mu et et et et et et al., al., al., al., al., al., 1999b) 1998) 1999b) 1999b) 1999b) 2004)

Styryl-pyrone Styryl-pyrone

(Sam et al., 1987) (Sam et al., 1987)

Furano-pyrone Furano-pyrone Styryl-pyrone Styryl-pyrone

(Colegate et al., 1990) (Colegate et al., 1990) (Ee et al., 1999) (Ee et al., 1999)

Table 1.4 (cont.): Styryl-lactones from the genus Goniothalamus Species and Compounds
Isoaltholactone (120) Goniothalamus scortechinii Goniothalamin (98) Goniothalamus sesquipedalis Goniodiol (106) Goniodiol diacetate (110) Goniothalamin (98) 5-Acetoxyisogoniothalamin oxide (103) Goniotriol (111) Goniothalamus tapis Arvensin (126) Goniothalamin (98) Isoaltholactone (120)

Type
Furano-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Furano-pyrone Styryl-pyrone Furano-pyrone

References
(Ee et al., 1999) (Zakaria et al., 1989) (Talapatra et al., 1985) (Talapatra et al., 1985) (Hasan et al., 1995) (Hasan et al., 1994) (Talapatra et al., 1985) (Ee et al., 2000) (Zakaria et al., 1989) (Colegate et al., 1990)

30

Goniothalamus umbrosus 5-Acetoxygoniothalamin (99) Dehydrogoniothalamin (101) Goniothalamin (98) Goniothalamus uvarioides 5-Acetylgoniothalamin (99) Goniothalamin (98) Goniothalamus velutinus Altholactone (119) Goniothalamin (98)

Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Styryl-pyrone Furano-pyrone Styryl-pyrone

(Ahmad and Din, 2002) (Ahmad and Din, 2002) (Ahmad and Din, 2002) (Ahmad et al., 1991) (Ahmad et al., 1991) (Ee, 1998) (Ee, 1998)

31

R
5

Ph

II

Ph

Compound Names
98 Goniothalamin

Absolu Substituti te Sourc ons config es .

A: R=H 6R GAM GAN GBO GCA GCH GDO GFU GGI GGR GHO GLE GMA GML GRI GSC GSE GTA GUM GUV

Reference
(Lan et al., 2003) (Tanaka et al., 1997) (Cao et al., 1998) (Hisham et al., 2000) (Li et al., 1997b) (Goh et al., 1995b) (Zakaria et al., 1989) (El-Zayat et al., 1985) (Chen and Yu, 1999) (Zhang et al., 1993) (Mu et al., 1998) (Sam et al., 1987) (Colegate et al., 1990) (Ee et al., 1999) (Zakaria et al., 1989) (Hasan et al., 1995) (Zakaria et al., 1989) (Ahmad and Din, 2002) (Ahmad et al., 1991) (Ee, 1998) (Ahmad and Din, 2002) (Ahmad et al., 1991) (Goh et al., 1995a)

99 5-Acetoxygoniothalamin 100 5-Hydroxygoniothalamin 101 Dehydrogoniothalamin

A: R=OAc

5S, 6S

GVE GUM GUV GDO GUM GCL

A: R=OH B

5S, 6S

{Ahmad, 2002 #182 {Ahmad, 2001 #303} Note: GAM=G. amuyon, GAN=G. andersonii, GBO=G. borneensis, GCA= G. cardiopetalus, GCH= G. cheliensis, GCL=G. clemensii, GDO=G. dolichocarpus, GFU=G. fulvus, GGI=G. giganteus, GGR=G. griffithii, GHO=G. howii, GLE=G, leiocarpus, GMA=G. macrophyllus, GML=

32

G. malayanus, GRI=G. ridleyi, GSC=G. scortechinii, GSE=G. sesquipedalis, GTA=G. tapis, GUM=G. umbrosus, GUV=G. uvaroides, GVE=G. velutinus

Figure 1.13: Styryl-pyrones of Goniothalamus.

33

R
5

O
7

H Ph

Compound Names
102 Goniothalamin oxide

Absolute Substituti configura ons tion

R=H 6R, 7S, 8S

Sourc es
GAM GAN GDO GMA GRI

Reference
(Lan et al., 2003) (Ee et al., 1998) (Goh et al., 1995b) (Sam et al., 1987) (Ee et al., 1999) (Peris et al., 2000) (Hasan et al., 1994) (Li et al., 1998)

103 5-Acetoxyisogoniothalamin oxide 104 Cheliensisin A

R=OAc

5S, 6S, 7R, 8R

GAR GSE

5R, 6S, 7R, GCH 8R 105 Howiinin A R=OCinnam 5S, 6R, 7S, GHO oyl 8S Note: GAM=G. amuyon, GAN=G. andersonii, GCH=G. cheliensis, GDO=G. dolichocarpus, GHO= G. howii, GMA=G. macrophyllus, GRI=G. ridleyi, GSE=G. sesquipedalis

R=OAc

Figure 1.13 (cont.): Styryl-pyrones of Goniothalamus.

34

R1
7

OR3 Ph

OR2

Compound Names
106 Goniodiol

Substituti ons
R1=R2=R3=H

Absolut Sourc e es config.

6R, 7R, 8R GAN GCA GDO GGI GGR GSE

Reference
(Ee et al., 1998) (Tanaka et al., 1997) (Hisham et al., 2003) (Goh et al., 1995b) (Fang et al., 1991b) (Talapatra et al., 1985) (Talapatra et al., 1985) (Mu et al., 1999b) (Wu et al., 1991) (Lan et al., 2003) (Zhang et al., 1999b) (Wu et al., 1992) (Lan et al., 2003) (Talapatra et al., 1985) (Talapatra et al., 1985) (Wu et al., 1992) (Lan et al., 2003) (Alkofahi et al., 1989) (Zhang et al., 1999b) (Talapatra et al., 1985) (Fang et al., 1990) (Chen and Yu, 1999) (Bermejo et al., 1998a) (Lan et al., 2003)

107 7-epiGoniodiol 108 7-Acetylgoniodiol 109 8-Acetylgoniodiol 110 Goniodiol diacetate 111 Goniotriol

R1=R2=R3=H R1=R3=H; R2=Ac R1=R2=H; R3=Ac R1=H; R2=R3=Ac R1=OH; R2=R3=H

6R, 7S, 8R 6R, 7R, 8R 6R, 7R, 8R 6R, 7R, 8R 5S, 6R, 7R, 8R

GLE GAM GGR GSE GAM GGR GSE GAM GGI GGR GSE

112 8-Acetylgoniotriol 113 Etharvendiol

R1=OH; 5S, 6R, GGI R2=H; R3=Ac 7R, 8R GGR R1=OEt; 5S, 6R, GAR R2=R3=H 7R, 8R 114 7,8-diepimer- R1=OH; 5S, 6R, GAM Goniotriol R2=R3=H 7S, 8S 115 8-MethoxyR1=R2=H; 6R, 7R, GAM (Lan et al., 2003) goniodiol R3=Me 8R 116 8-ChloroR1=R2=H; 6R, 7R, GAM (Lan et al., 2003) goniodiol R3=Cl 8R 117 Leiocarpin C R1=R2=R3=H 6R, 7R, GLE (Mu et al., 1999b) 8R 4-hydroxy; 3,4 dihydro Note: GAM=G. amuyon, GAN=G. andersonii, GBO=G. borneensis, GCA= G. cardiopetalus, GCH= G. cheliensis, GDO=G. dolichocarpuss, GFU=G. fulvus, GGI=G. giganteus, GGR=G. griffithii, GHO=G. howii, GMA=G. macrophyllus, GML=G. malayanus, GRI=G. ridleyi, GSC=

35

G. scortechinii, GSE=G. sesquipedalis, GTA=G. tapis, GUV=G. uvaroides, GVE=G. velutinus

Figure 1.13 (cont.): Styryl-pyrones of Goniothalamus.

36

OH OH
7

Ph

OH

Compound Names
118 Garvensintriol

Absolute configurat Sources ion

5S, 6R, 7S, 8S G. arvensis

Reference
(Bermejo et al., 1998a)

Figure 1.13 (cont.): Styryl-pyrones of Goniothalamus.

7a

Ph O O
3a 3

OR

Compound Names
119 Altholactone =goniothalenol

Absolut Substituti e ons config.

R=H 2R, 3R, 3aR, 7aS

Sources
GAR GGI GGR GVE

Reference
(Peris et al., 2000) (Bermejo et al., 1995) (El-Zayat et al., 1985) (Chen and Yu, 1999) (Ee, 1998) (Bermejo et al., 1995) (Khan et al., 1998) (Zhang et al., 1999b) (Ee et al., 1999) (Colegate et al., 1990) (Colegate et al., 1990) (Colegate et al., 1990) (Bermejo et al., 1999) (Bermejo et al., 1999)

120 Isoaltholactone

R=H

2R, 3S, 3aR, 7aS

GAR GGN GGR GRI GML GMO GTA

121 2-epiAltholactone 122 3-Acetylaltholactone

R=H R=Ac

2S, 3R, 3aR, 7aS 2R, 3R, 3aR, 7aS

GAR GAR

37

Note: GAR=G. arvensis, GGI=G. giganteus, GGN= G. grandiflorus, GGR=G. griffithii, GML= G. malayanus, GMO=G. montanus, GRI=G. ridleyi, GTA=G. tapis

Figure 1.14: Furano-pyrones of Goniothalamus.

38

R
7

H
7a

O Ph OH

3a

Compound Names
123 Goniofupyrone

Substituti Absolute ons config.

R=OH 2R, 3R, 3aS, 7aS, 7R 2R, 3R, 3aR, 7aS

Sourc es
GCA GGI GAR GGR

Reference
(Hisham et al., 2003) (Fang et al., 1991a) (Bermejo et al., 1995) (Chen and Yu, 1999) (Bermejo et al., 1997)

124 Goniotharvensin 125 Etharvensin

R=H

2R, 3R, GAR 3aS, 7aS, 7R 126 Arvensin R=OH 2R, 3R, GAR (Bermejo et al., 3aS, 7aR, GTA 1999) 7R (Ee et al., 2000) Note: GAR=G. arvensis, GCA=G. cardiopetalus, GGI=G. giganteus, GTA=G. tapis

R=OEt

H H

Ph

H O

OH

Compound Names
127 Cardiopetalolactone

Sources
G. cardiopetalus

Reference
(Hisham et al., 2000)

Figure 1.14 (cont.): Furano-pyrones of Goniothalamus.

39

O
6

OR Ph

OH

Compound Names
128 Goniofufurone

Substituti ons
R=H

Absolut Sourc e es config.

4R, 5S, 6S, 7R, 8R GAR GBO GCA GCH GGI GGR

Reference
(Bermejo et al., 1998a) (Cao et al., 1998) (Hisham et al., 2003) (Wang et al., 2001) (Fang et al., 1990) (Chen and Yu, 1999) (Fang et al., 1991b)

129 8-epiGoniofufurone

4R, 5S, GGI 6S, 7R, 8S 130 8-AcetylR=Ac 4R, 5S, GGR (Zhang et al., goniofufurone 6S, 7R, 1999b) 8R Note: GAR=G. arvensis, GBO=G. borneensis, GCA=G. cardiopetalus, GCH=G. cheliensis, GGI= G. giganteus, GGR=G. griffithii

R=H

Figure 1.15: Furano-furones of Goniothalamus.

4

O Ph
7

25

R1 OR2

Compound Names
131 Goniopypyrone

Substituti ons
R1=OH; R2=H

Absolute Sourc configurat es ion

4S, 5S, 6R, 7R, 8S GCA GGI GGR GAM GGI GGR GAN GDO GGR GLE

Reference
(Hisham et al., 2000) (Fang et al., 1990) (Zhang et al., 1999b) (Lan et al., 2003) (Fang et al., 1991b) (Chen and Yu, 1999) (Ee et al., 1998) (Goh et al., 1995b) (Zhang et al., 1999b) (Mu et al., 1999b)

132 5-Deoxygoniopypyrone 133 5-Deoxyisogoniopypyrone 134 Leiocarpin A

R1=R2=H

4R, 6R, 7S, 8S

R1=R2=H

4R, 6R, 7S, 8R 4R, 6R, 7S,

R1=R2=H

40

8R 135 7-AcetylR1=OH; 4S, 5S, 6R, GGR (Zhang et al., gonioR2=Ac 7R, 8S 1999b) pypyrone Note: GAM=G. amuyon, GAN=G. andersonii, GCA= G. cardiopetalus, GDO=G. dolichocarpus, GGI= G. giganteus, GGR=G. griffithii, GLE=G. leiocarpus. Some numbering systems are not consistent with this structure

Figure 1.16: Pyrano-pyrones of Goniothalamus.

H HO Ph
6

HO
2

OH HO H
E

HO H O O

O OH
Z

O Ph O

Ph OH OH

I Compound Names
136 Goniobutenolide A

II Absolu te config.
I: Z

Sourc es
GBO GGI

Reference

(Cao et al., 1998) (Fang et al., 1991a) 137 Goniobutenolide I: E GBO (Cao et al., 1998) B GGI (Fang et al., 1991a) 138 Cardiobutanolide II GCA (Hisham et al., 2003) Note: GBO=G. borneensis, GCA=G. cardiopetalus, GGI=G. giganteus

Figure 1.17: Butenolides of Goniothalamus.

HO R2O R1
7

OH Ph O O

Compound Names

Substitutio ns

Config.

Sourc es

Reference 41

139 Gonioheptolide A

cis/cis/trans GGI (Fang et al., / 1993) trans/ 140 Gonioheptolide R1=OH; R2=Et cis/cis/trans GGI (Fang et al., B / 1993) trans/ 141 Almuheptolide R1=OEt; R2=Et trans/cis/tra GAR (Bermejo et al., A ns/ 1998b) trans/ 142 Almuheptolide R1=H; R2=Et cis/trans/tra GAR (Bermejo et al., B ns/ 1998b) Note: GBO=G. borneensis, GCA=G. cardiopetalus, GGI=G. giganteus

R1=OH; R2=Me

Figure 1.18: Heptolides of Goniothalamus.

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OH

O Ph OH O

Ph

Compound Name
143 Leiocarpin B

Source
G. leiocarpus

Reference
(Mu et al., 1999a; Mu et al., 1999b)

Figure 1.19: A hybrid of a styryl-pyrone and a flavanone from Goniothalamus.

H O H HO H O O H O O

Compound Name
144 Leiocarpin E

Source
G. leiocarpus

Reference
(Mu et al., 2004)

Figure 1.20: Styryl-pyrone dimer from Goniothalamus.

43