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Molecules 2019, 24(9), 1842; https://doi.org/10.3390/molecules24091842

Review
A Review on Daphnane-Type Diterpenoids and Their Bioactive Studies
1
College of Chinese Medicine Material, Jilin Agricultural University, Changchun 130118, China
2
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and PekingUnion Medical College, Beijing 100193, China
3
Xinjiang Institute of Chinese and Ethnic Medicine, Urumqi 830002, China
4
College of Life Science and Technology, Xinjiang University, Urumqi 830046, China
*
Correspondence: [email protected] (G.-X.M.); [email protected] (J.Z.)
These authors contributed equally to this work.
Received: 16 April 2019 / Accepted: 7 May 2019 / Published: 13 May 2019

Abstract

:
Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019.
Keywords:
daphnane; diterpenoid; cytotoxic activities

1. Introduction

Since the first daphnane diterpenoid characterized by a macrolactone motif was isolated from Trigonostemon reidioides [1], the daphnane diterpenoids have attracted the interest of many researchers because of their significant bioactive activities. Until now, nearly 200 natural products of daphnane-type diterpenoids have been isolated and identified, and they have shown good biological activities, including anti-HIV, anti-cancer, anti-leukemia, anti-hyperglycemic [2], neurotropic [3], insecticidal and cytotoxic [4] effects. Due to their rich pharmacological activities, especially strong anti-HIV activity and small cytotoxicity, daphnane-type diterpenoids have been employed in a range of clinical applications for a variety of clinical uses [5,6]. Studies have found that the natural daphnane-type diterpenoids usually embrace a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while a special group also have a characteristic orthoester motif connected to C-9, C-13, and C-14. The daphnane-type diterpenoids can be categorized into five types (Figure 1): 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the substitution pattern of ring A and the oxygen-containing functions at rings B and C. Besides, 6-epoxy daphnane diterpenoids usually have a C-6α epoxy structure in ring B; resiniferonoids usually have an α-β unsaturated ketone structure in ring A; genkwanines usually have an α-β saturated ketone structure in ring A, but without a C-6α epoxy structure in ring B; 1-alkyldaphnanes usually have a saturated ring A, and a large ring between the end of the orthoester alkyl chain and C-1 of ring A; and rediocides usually have a 12-carbon macrolide structure between C-3 and C-16, and have a special C-9, C-12, and C-14 orthoester structure. The variety of daphnane-type diterpenoid structures have continued to widen with the discovery of unusual variations with the well-established skeleton. Owing to the unique skeleton and remarkable bioactive activities, daphnane-type diterpenoids have attracted many synthetic endeavors to construct a core structure. However, few papers have reported on the total synthesis of daphnane diterpenoids—isolation from natural plants is still the only source of obtaining daphnane diterpenoids. Considering the extensive interest in daphnane-type diterpenoids, we reviewed the structural and bioactive activities of daphnane-type diterpenoids, with an emphasis on the recent progress in structure identification and bioactive evaluation.

2. Occurrence

Natural daphnane-type diterpenoids are mainly distributed in species belonging to the Thymelaeaceae or Euphorbiaceae families (Table 1). These plants grow mainly in tropical and subtropical regions of Asia [7]. Previous chemical investigations on such species have led to the isolation of a number of structurally diverse diterpenoids [8]. Various daphnane-type diterpenoids have been isolated from some parts of the following plants: The twigs and leaves of Trigonostemonthyrsoideum, the roots of Trigonostemonreidioides, the stems of Trigonostemon lii, the twigs and leaves of Trigonostemonchinensis Merr, the stem barks of Daphne giraldii, the air-dried roots of Euphorbia fischeriana, the stems of D. acutiloba, the roots of Lasiosiphonkraussianus, the flower buds of Daphne genkwa, and the roots of Maprouneaafricana Muell. Arg., Trigonostemonxyphophylloides, Wikstroemiaretusa, Trigonostemonhowii, and Stellerachamaejasme L., and so on [9].

3. Species of Daphnane-Type Diterpenoids and Their Bioactive Activities

3.1. 6-Epoxy DaphnaneDiterpenoids

6-epoxy daphnane diterpenoids featurea C-6α epoxy structure in ring B and, occasionally, an α-β unsaturated ketone structure in ring A. In most cases, there is also a C-5β hydroxyl group and a C-20 hydroxyl group in ring B (Figure 2, Table 2). Compounds acutilobins A–G (15, 65, 66), wikstroemia factor M1 (74), genkwanineVIII (69), gniditrin (14), gnididin (15), gnidicin (13), daphnetoxin (6), yuanhuajine (50), kirkinine (24), excoecaria factor O1 (8), excoecaria toxin (7), and 14′-ethyltetrahydrohuratoxin(51) have been obtained from the stems of D. acutiloba. Acutilobins A–G have been shown to exhibit significant anti-HIV-1 activities, with EC50 below 1.5 μM [10]. Trigoxyphins A (32), B (59), and trigothysoid M (63) have been isolated from the twigs and leaves of Trigonostemonthyrsoideum. These compounds have been evaluated for anti-HIV activity by an assay of the inhibition of the cytopathic effects of HIV-1 and cytotoxicity against C8166 cells. However, only trigoxyphin A expressed weak anti-HIV-1 activity [11]. Compounds huratoxin (20) and wikstroelides A–D (3740), H–J (4142, 56), and L–N (43, 5758) have been obtained from the fresh bark of Wikstroemiaretusa. The orthoester compounds wikstroelides D and H, with palmitic acid at their 20-hydroxyl site, have shown the weakest cytotoxic activity [12]. Antitumor compounds genkwanin I (64) and orthobenzoate 2 (70) have been isolated from the flower buds of Daphne genkwa. Genkwanin I has been shown to be a potent cell growth inhibitor constituent [13]. Active ingredients genkwadane D (9), yuanhuadine (47), yuanhuafine (45), yuanhuacine (49), yuanhuahine (44), yuanhuapine (61), genkwadaphnine (10), isoyuanhuadine (23), and genkwanine M (67) were obtained from the flower buds of Daphne genkwa. Among them, yuanhuadine, genkwadaphnine, yuanhuafine, yuanhuapine, and genkwanine M have exhibited the strongest cytotoxic activities against the HT-1080 cell line (IC50 < 0.1 µM) [14]. Maprouneacin (76) has been isolated from the roots of Maprouneaafricana Muell. Arg, and has shown potent glucose-lowering properties when administered via the oral route. [15]. The compound trigonostempene C (71) has been obtained from the twigs and leaves of Trigonostemonthyrsoideum, but did not show any significant activity [16]. Compounds yuanhualine (46) and yuanhuagine (48) have been isolated from Daphne genkwa. In the analysis of signal transduction molecules, yuanhualine and yuanhuagine appear to suppress the activation of Akt, STAT3 and Src in human lung cancer cells, and also exert potent antiproliferative activity against anticancer-drug resistant cancer cells [17]. Gnidilatidin (17), gnidilatidin-20-palmitate (18), 1, 2α-dihydrodaphnetoxin (62), genkwadaphnin-20-palmitate (11) and gnidicin-20-palmitate (19) have successfully been obtained from the stems of D. oleoidesSchreber ssp. oleoides [18]. Trigoxyphins J and K (3334) have been isolated from the stems of Trigonostemonxyphophylloides, and subsequently shown to be inactive against three tumor cell lines, specifically thehuman chronic myelogenous leukemia cell line (K562), the human gastric carcinoma cell line (SGC-7901), and human hepatocellular carcinoma (BEL-7402) (IC50 value > 10 μM) [19]. Genkwanine N (68) has been obtained from the dried flower buds of Daphne genkwa, and the compound with esterification of the 20-hydroxyl has shown weak toxicity [20]. Trigonosin B (73) has beenisolated from the roots of Trigonostemonthyrsoideum [21], whilecompounds hirseins A and B (2122) have been isolated from Thymelaeahirsuta. Hirseins A and B have shown inhibition of melanogenesis in B16 murine melanoma cells [22]. Glabrescin(12) and Montanin (26) have been obtained from Neoboutoniaglabrescens [23]. Kirkinine D (25) and synaptolepisfactor K7 (28) have been isolated from the S.kirkii [24]. Wikstrotoxin C (35) has been isolated from W.monticola. The compound 2α-dihydro-20-palimoyldaphnetoxin (52) has been isolated from the D.tangutica, while gnidiglaucin (16) has been obtained from P.elongata [24]. Trigoxyphin C (60) has been obtained from T.xyphophylloides, and tested against BEL-7402 cells (human hepatocellular carcinoma), where in it has been shown to be inactive (IC50 value > 10 µM was defined as inactive) [25]. Trigonosin A (72) has been isolated from T.thyrsoideum, and shown to exhibitin significant inhibitory activity against specific tumor cells (IC50 >10 μM) [21]. Isovesiculosin and vesiculosin (5455) have been isolated from D.vesiculosum [26]. Genkwanine O (75) has been obtained from D.genkwa. Compound daphnegiraldigin (53) has been isolated from the stem barks of Daphne giraldii [27]. Simplexin(27) has been obtained from Stellerachamaejasme L. [5]. Compounds trigochinins G–I (2931) have been isolated from the twigs and leaves of Trigonostemonchinensis Merr [28].

3.2. Resiniferonoids

Relative to 6-epoxy daphnane diterpenoids, there is no C-6α epoxy structure in ring B forresiniferonoids. However, resiniferonoids do possess an α-β unsaturated ketone structure in ring A (Figure 3, Table 3). Compounds 4β, 9α, 20- trihydroxy- 13, 15- secotiglia- 1,6- diene- 3,13- dione 20-O-β-d- [6-galloyl] glu- copyranoside (86) and euphopiloside A (84) have beenisolated from the air-dried roots of Euphorbia fischeriana, and display moderate inhibitory effects against α-glucosidase in in-vitro bioassays [29]. Yuanhuatine (78) has been isolated from the flower buds of Daphne genkwa [14]. Compounds daphneresiniferins A and B (8081) have been obtained from the flower buds of Daphne genkwa. A study found that daphneresiniferin A was able to dependently inhibit melanin production [30]. Genkwanine L (77) has been isolated from the bud of Daphne genkwa [31]. Euphopiloside B (83), langduin A (85) and phorbol (87) have been obtained from the Euphorbia Pilosa [32], while compounds genkwadane A (79) and yuanhuaoate B (82) have been isolated from the flower buds of Daphne genkwa [14].

3.3. Genkwanines

Relative to 6-epoxy daphnane diterpenoids and resiniferonoids, genkwanines have an α-β saturated ketone structure in ring A, but do not possess a C-6α epoxy structure in ring B (Figure 4, Table 4). Compound trigoxyphin H (100) has been isolated from the twigs of Trigonostemonxyphophylloides [33]. The active ingredients trigothysoids A–L (122124, 9699, 139141, 131,128), trigochinins A–E (145146, 130, 147148), andtrigonothyrins D, E (143144) and G (121) have been obtained from the twigs and leaves of Trigonostemonthyrsoideum. These compounds have been evaluated for their anti-HIV activity usingan assay to determine their inhibition of the cytopathic effects of HIV-1 and their cytotoxicity against C8166 cells. Amongst them, trigothysoid A and L exhibited moderate anti-HIV-1 activity; andtrigothysoid C and K andtrigochinins A, B and D expressed weak anti-HIV-1 activity [11]. Trigolins A–G (132138) and trigonothyrin F (107) have been isolated from the stems of Trigonostemon lii. Trigolins A, G, H, and K have been shown to exhibit modest anti-HIV-1 activity with EC50 values of 2.04, 9.17, 11.42, and 9.05l µg/mL, respectively [34]. Compound trigochinin F (149) has been obtained from the twigs and leaves of Trigonostemonchinensis Merr, and has shown strong inhibition of HL-60 tumor cell lines [28]. Trigonothyrins A–C (125127) have been isolated from the stems of Trigonostemonthyrsoideum [6]. Among them, trigonothyrin C has shown significant activity to prevent the cytopathic effects of HIV-1 in C8166 cells, with an EC50 value of 2.19 µg/mL [35]. Compounds genkwanines F, I, and J (93, 113, 114) have been isolated from the flower buds of Daphne genkwa [14]. Genkwanine H (95) has been obtained from the flower buds of Daphne genkwa, and the compound has been shown to dependently inhibit melanin production [30]. Compounds trigonostempenes A (150) and B (129) have been isolated from the twigs and leaves of Trigonostemonthyrsoideum. Studies have shown that the discovery of these NO inhibitory daphnane diterpenoids—including compound trigonostempene A—which possess IC50 values comparable topositive controls may have the potential to be developed as anti-neuroinflammatory agents for alzheimer disease (AD) and other related neurological disorders [16]. Most inhibitors of acetylcholinesterase (AchE) are alkaloids that often possess several side effects, whereas these daphnane-type diterpenoids do not belong to the class of alkaloids, and therefore they may constitute novel active AChE inhibitors with fewer side effects. It is important to search for new AChE inhibitors not belonging to this structural class [36,37]. Genkwanines A–E (8892), G (94), I (113), and K (115) have been obtained from the bud of Daphne genkwa. Among these compounds, genkwanine D has been shown to exhibit strong activity to inhibit the endothelium cell HMEC at IC50 levels of 2.90–15.0 μM [31]. Compounds trigoxyphins U and W (105116) have been isolated from the twigs of Trigonostemonxyphophylloides. Trigoxyphin W has shown modest cytotoxicity against BEL-7402, SPCA-1 and SGC-7901, with IC50 values of 5.62, 16.79 and 17.19 µM, respectively [33]. Trigonosins C–D (106, 142) have been obtained from the roots of Trigonostemonthyrsoideum [21]. Trigoxyphin I (104) has been isolated from the Trigonostemonxyphophylloides [38]. Compounds trigohownins D and E (101102), and trigohownins A–C (108110) and F–I (117120) have been obtained from the Trigonostemonhowii. Among them, trigohownins A and D have been shown to exhibit moderate cytotoxic activity against the HL-60 tumor cellline, with IC50 values of 17.0 and 9.3 μM, respectively [39]. Trigoxyphins D–F (111112, 103) have been isolated from Trigonostemonxyphophylloides, with all three compounds found to be inactive against BEL-7402 cells (IC50 value > 10 µM) [25].

3.4. 1-Alkyldaphnanes

1-alkyldaphnanes have a large ring between the end of the orthoester alkyl chain and C-1 of ring A (Figure 5, Table 5). Pimelea factors S6 (168) and S7 (169) have been isolated from the flower buds of Wikstroemiachamaedaphne and have shown moderate cytotoxic activities against human myeloid leukemia HL-60, hepatocellular carcinoma SMMC-7721, lung cancer A549, breast cancer MCF-7, and colon cancer SW480 [1]. Compound pimelea factor P2 (155) has been obtained from the fresh bark of Wikstroemiaretusa, and has been shown to exhibit cytotoxicity in 10 cell lines (including HeLa, HepG2, HT-1080, HCT116, A375-S2, MCF-7, A549, U-937, K562 and HL60 cell lines) [14]. Wikstroelides E–G, K and O (163167) have been isolated from the fresh bark of Wikstroemiaretusa. Among them, compound wikstroelide E has been shown to exhibit the highest activity against cell lines PC-6 (human lung cancer cell line) and P388 (mouse leukaemia cell line), followed by wikstroelides A and J, which have the orthoester group without a fatty acid at the 20-hydroxyl [12]. Compounds stelleralides A–C (151152, 174) and gnidimacrin (153) have been isolated from the Stellerachamaejasme L. [5]. Genkwadane B (154), pimelotides A and C (170, 172), and genkwadane C (156) have been isolated from the flower buds of Daphne genkwa [14]. Compounds wikstroelides R–T (157159) have been obtained from the flower buds of Wikstroemiachamaedaphne. Wikstroelide R has been shown to have moderate cytotoxic activities against human cancer cell lines [1]. Compounds kirkinines B, C, and E (160162) were isolated from Synaptolepiskirkii. Pimelotides B and D (171, 173) have beenobtained from Pelongata [40].

3.5. Rediocides

Rediocides usually have a 12-carbon macrolide structure between C-3 and C-16, and have a special C-9, C-12, and C-14 orthoester structure (Figure 6, Table 6). The active compounds trigothysoids N–P (182184), rediocides A, C, and F (176177, 179), and trigonosin F (181) have been obtained from the twigs and leaves of Trigonostemonthyrsoideum. Amongst them, compounds trigothysoid N, rediocides A, C, and F, and trigonosins F have shownpotent anti-HIV-1 activity, with EC50 values ranging from 0.001 to 0.015 nM. Additionally, trigothysoid O has been shown to exhibit moderate anti-HIV-1 activity [11], while rediocide A has shown potent activities against mosquito larvae in an in-vitro assay study and against fleas (Ctenocephalides felis) in an artificial membrane feeding system, exhibiting LD90 values of 1 and 0.25 ppm, respectively [39]. Trigochilides A and B (175, 186) have been isolated from the twigs and leaves of Trigonostemonchinensis Merr. Trigochilide A has shown modest cytotoxicity against HL-60 (human leukemia) and BEL-7402 (human hepatoma), with demonstrated IC50 values of 3.68 and 8.22 µM, respectively, whereas compound trigochilide B has only been shown to exhibit weak cytotoxicity against two tumor cell lines, with IC50 values of 33.35 and 54.85 µM [1]. Compound rediocide E (178) has been obtained from the roots of Trigonostemonreidioides, and has shown significant acaricidal activity on D. pteronyssinus [40]. Trigonosin E (180) and trigonostempene D (185) have beenisolated from the twigs and leaves of Trigonostemonthyrsoideum [16,21]. Rediocides B, G, and D (187189) have been isolated from the Trigonostemonreidioides, and have been evaluated for their insecticidal properties in an anti-flea artificial membrane feeding assay (as detailed earlier). In this assay, rediocides B and D exhibited LD90 values of 0.25 and 0.5 ppm, respectively, and thus were equipotent with rediocide A (LD90 0.25 ppm) [41].

4. Conclusions

It can be concluded that the bioactive activities of daphnane-type diterpenoids is obviously related to structure types. The most important points of them are the following: (1) The orthoester groups at C-9, C-13 and C-14 are essential to the cytotoxic activity. Daphnane-type diterpenoids with orthoester groups at C-9, C-13, and C-14 usually have stronger activity than daphnane-type diterpenoids with orthoester groups at C-9, C-12, and C-14 or C-12, C-13 and C-14. The absence of the orthoester group is unhelpful to the cytotoxic activity. (2) Specific to the 6-epoxyl groups, free 20-hydroxyl and 3-carbonyl are important for their activities. (3) Side chains at C-10 are crucial for cytotoxic activities. Generally speaking, long C-10 alkyl chains are more important than phenyl at C-10. Interestingly, the structure with macro-lactones exhibited much stronger activity than the others. Due to the rich activities of daphnane-type diterpenoids, researchers have not stopped exploring and researching such compounds and their bioactive activities from plants.

Funding

This research was funded by the National Natural Science Foundation of China [grant number 81860759].

Conflicts of Interest

There is no conflict of interest associated with the authors of this paper.

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Sample Availability: Samples of the compounds are available from the authors.
Figure 1. The kinds of daphnane-type diterpenoids skeleton.
Figure 1. The kinds of daphnane-type diterpenoids skeleton.
Molecules 24 01842 g001
Figure 2. Eight types (AH) of 6-epoxy daphnane skeletons.
Figure 2. Eight types (AH) of 6-epoxy daphnane skeletons.
Molecules 24 01842 g002
Figure 3. Seven types (IO) of resiniferonoids skeletons.
Figure 3. Seven types (IO) of resiniferonoids skeletons.
Molecules 24 01842 g003
Figure 4. Eight types (PW) of genkwanines skeletons.
Figure 4. Eight types (PW) of genkwanines skeletons.
Molecules 24 01842 g004
Figure 5. Four types (X1X4) of 1-alkyldaphnanes skeletons.
Figure 5. Four types (X1X4) of 1-alkyldaphnanes skeletons.
Molecules 24 01842 g005
Figure 6. Five types (Y1Y5) of rediocides skeletons.
Figure 6. Five types (Y1Y5) of rediocides skeletons.
Molecules 24 01842 g006
Table 1. The species of daphnane-type diterpenoids.
Table 1. The species of daphnane-type diterpenoids.
Types of DiterpenoidsSpeciesMedication Site
6-epoxy daphnane diterpenoidsD. acutilobaUsually their effective part is roots, stems, twigs and leaves, flower buds, fresh bark.
Trigonostemonthyrsoideum
Wikstroemiaretusa
Daphne genkwa
D. oleoidesSchreber ssp. oleoides
Trigonostemonxyphophylloides
Thymelaeahirsuta
Neoboutoniaglabrescens
S.kirkii
W.monticola
D.tangutica
P.elongata
T.xyphophylloides
T.thyrsoideum
D.vesiculosum
Stellerachamaejasme L.
Trigonostemonchinensis Merr
ResiniferonoidsEuphorbia fischerianaGenerally, the roots and flower budsistheir effective part.
Daphne genkwa
Euphorbia pilosa
GenkwaninesTrigonostemonxyphophylloidesUsually their effective part isroots, stems, twigs and leaves, flower buds.
Trigonostemonthyrsoideum
Trigonostemon lii
Trigonostemonchinensis Merr
Daphne genkwa
Trigonostemonhowii
1-alkyldaphnanesWikstroemiachamaedaphneUsually, the flower buds and fresh bark is their effective part.
Wikstroemiaretusa
Stellerachamaejasme L.
Daphne genkwa
Synaptolepiskirkii
P.elongata
RediocidesTrigonostemonthyrsoideumGenerally, their effective part is roots, twigs and leaves.
Trigonostemonchinensis Merr
Trigonostemonreidioides
Table 2. Reported structures of 6-epoxy daphnane skeletons.
Table 2. Reported structures of 6-epoxy daphnane skeletons.
No.NameR1R2R3R4R5Type
1Acutilobin AHOHPhOCO(CH=CH)2COC(CH2)2CH3A
2Acutilobin BHOHPhOCO(CH=CH)3CHCH2CH3OHA
3Acutilobin CHOH(CH=CH)3(CH2)2CH3OCOCH=CHPhCH3OHA
4Acutilobin DHOH(CH=CH)2(CH2)4CH3OCOCH=CHPhCH3OHA
5Acutilobin EHOHPhOCOCH=CHPhCH3OHA
6DaphnetoxinHOHPhHA
7Excoecaria toxinHOH(CH=CH)2(CH2)4CH3HA
8Excoecaria factor O1HOH(CH=CH)3(CH2)2CH3HA
9Genkwadane DHOH(CH=CH)2(CH2)4CH3OCOCH(CH3)2A
10GenkwadaphnineHOHPhOBzA
11Genkwadaphnin-20-palmitateHOCO(CH2)14CH3PhOCOPhA
12GlabrescinHOCOCH2(CH2)13CH3 (CH2)10CH3HA
13GnidicinHOHPhOCOCH=CHPhA
14GniditrinHOHPhOCO(CH=CH)3(CH2)2CH3A
15GnididinHOHPhOCO(CH=CH)2(CH2)4CH3A
16GnidiglaucinHOH(CH2)8CH3OAcA
17GnidilatidinHOH(CH=CH)2(CH2)4CH3OCOPhA
18Gnidilatidin-20-palmitateHOCO(CH2)14CH3(CH=CH)2(CH2)4CH3OCOPhA
19Gnidicin-20-palmitateHOCO(CH2)14CH3PhOCOCH=CHPhA
20HuratoxinHOH(CH=CH)2(CH2)8CH3HA
21Hirsein AHOHCH=CH(CH2)4CH3OCOCH=CHPhA
22Hirsein BHOHCH=CH(CH2)4CH3OCOCH=CHPhOHA
23IsoyuanhuadineHOH(CH=CH)2(CH2)4CH3OAcA
24KirkinineHOHCH=CH(CH2)12CH3OAcA
25Kirkinine DHOH(CH=CH)3(CH2)2CH3OAcA
26MontaninHOH(CH2)10CH3HA
27SimplexinHOH (CH2)8CH3HA
28Synaptolepisfactor K7HOHCH=CH(CH2)12CH3HA
29Trigochinin GHHPhOCOCH2CH(CH3)2A
30Trigochinin HHHPhOCOC6H4(4-OH)A
31Trigochinin IHHPhOCOC6H3(3-OMe)(4-OH)A
32Trigoxyphin AHHPhOBzA
33Trigoxyphin J HOHCH3OCO(CH2)14CH3A
34Trigoxyphin KHHPhOBzA
35Wikstrotoxin C Molecules 24 01842 i001OH(CH=CH)2(CH2)4CH3OAcA
36Wikstrotoxin DHOHn-C9H19HA
37Wikstroelide AHOH(CH=CH)2(CH2)8CH3OAcA
38Wikstroelide BHOH(CH=CH)2(CH2)9CH3OAcA
39Wikstroelide CHO-trans-5-pentadecenoic acid(CH=CH)2(CH2)8CH3OAcA
40Wikstroelide DHO-palmitic acid(CH=CH)2(CH2)8CH3OAcA
41Wikstroelide HHOH(CH=CH)2(CH2)6CH3OAcA
42Wikstroelide IHO-palmitic acid(CH=CH)2(CH2)9CH3OAcA
43Wikstroelide LHOH(CH=CH)2(CH2)8CH3OAcA
44YuanhuahineHOH(CH=CH)2(CH2)4CH3OCOCH2CH3A
45YuanhuafineHHPhOAcA
46YuanhualineHOH(CH=CH)2(CH2)4CH3OCO(CH2)2CH3A
47YuanhuadineHOH(CH=CH)2(CH2)4CH3OAcA
48YuanhuagineHOH(CH=CH)(CH2)2CH3OCOCH3A
49YuanhuacineHOH(CH=CH)2(CH2)4CH3OBzA
50YuanhuajineHOH(CH=CH)3(CH2)2CH3OBzA
5114′-ethyltetrahydrohuratoxinHOH(CH2)14CH3HA
522α-dihydro-20-palimoyldaphnetoxinHOHCH=CH(CH2)6CH3OAcA
53DaphnegiraldiginHOHCOPhHHB
54IsovesiculosinAcAcAcCO(CH=CH)2(CH2)4CH3HB
55VesiculosinHHCO(CH=CH)2(CH2)4CH3HHB
56Wikstroelide JHHCO(CH=CH)2(CH2)8CH3HOAcB
57Wikstroelide MHHCO(CH=CH)2(CH2)8CH3HHB
58Wikstroelide NHHCO(CH=CH)2(CH2)9CH3HHB
59Trigoxyphin BHHOBzC
60Trigoxyphin CAcHOBzC
61YuanhuapineHOHOAcC
621,2α-dihydrodaphnetoxinHOHHC
63Trigothysoid MD
64Genkwanin IE
65Acutilobin FCO(CH=CH)3(CH2)2CH3OHHF
66Acutilobin GCOCH=CHPhOHHF
67Genkwanine MHOBzHF
68Genkwanine NBzOHHF
69GenkwanineVIIICOPhOHHF
70Orthobenzoate 2HOHHF
71Trigonostempene CHHOHF
72Trigonosin AHHOBzF
73Trigonosin BHOHOBzF
74Wikstroemia factor M1CO(CH=CH)2(CH2)4CH3OHHF
75Genkuanine OG
76MaprouneacinH
Table 3. Reported structures of resiniferonoids skeletons.
Table 3. Reported structures of resiniferonoids skeletons.
No.NameRType
77Genkwanine LOAcI
78YuanhuatineOBzI
79Genkwadane AJ
80Daphneresiniferin AMeK
81Daphneresiniferin BPhK
82Yuanhuaoate BL
83Euphopiloside BM
84Euphopiloside A Molecules 24 01842 i002N
85Langduin AHN
864β,9α,20-trihydroxy-13,15-secotiglia-1,6-diene-3,13-dione20-O-β-d-[6-galloyl]glu-copyranoside Molecules 24 01842 i003N
87PhorbolO
Table 4. Reported structures of genkwanines skeletons.
Table 4. Reported structures of genkwanines skeletons.
No.NameR1R2R3R4R5R6R7R8Type
88Genkwanine AHHHOHCH2OHHPhHP
89Genkwanine BCO(CH=CH)2(CH2)4CH3HHOHCH2OHHPhHP
90Genkwanine CCO(CH=CH)3(CH2)2CH3HHOHCH2OHHPhHP
91Genkwanine DBzHHOHCH2OHHPhHP
92Genkwanine EHHHOHCH2OCO(CH=CH)3(CH2)2CH3HPhHP
93Genkwanine FHHHOHCH2OCO(CH=CH)2(CH2)4CH3HPhHP
94Genkwanine GHHHOHCH2COO(CH=CH) (CH2)6CH3HPhHP
95Genkwanine HHHHOHCH2OBzHPhHP
96Trigothysoid DHHHOHMeHMeOBzP
97Trigothysoid EAcHHOHMeHMeOBzP
98Trigothysoid FHHAcOHMeHMeOBzP
99Trigothysoid GAcHBzOHMEHMeOBzP
100Trigoxyphin HAcHAcOCOPhMeAcPhOAcP
101Trigohownin DAcBzAcOHMeAcPhOAcP
102Trigohownin EAcHBzOHMeAcMeOBzP
103Trigoxyphin FAcHAcOBzMeAcPhOHP
104Trigoxyphin IAcHAcOCOPhMeAcPhAcP
105Trigoxyphin UAcHAcMeOCOPhAcMEOCOPhP
106Trigonosin CHHHOHMeHPhOBzP
107Trigonothyrin FHHHOHMeHPhHP
108Trigohownin AOAcOHBzOAcOHQ
109Trigohownin BOBzOACHOAcOHQ
110Trigohownin COHOACBzOHOHQ
111Trigoxyphin DOHOACBzOAcOHQ
112Trigoxyphin EHOACBzOAcOAcQ
113Genkwanine IHHOHCH2OHHBzHHR
114Genkwanine JHHOHCH2OCO(CH=CH)2(CH2)4CH3HBzHHR
115Genkwanine KHHOHCH2BzHBzHHR
116Trigoxyphin WAcAcMeOCOPhHHCOPhHR
117Trigohownin FAcAcOBzMeAcHBzOHR
118Trigohownin GAcAcOBzMeAcAcBzOHR
119Trigohownin HAcAcOBzMeAcBzAcOHR
120Trigohownin IAcBzOHMeAcAcBzOHR
121Trigonothyrin GAcHOCOPhS
122Trigothysoid AHHOBzS
123Trigothysoid BAcBzOBzS
124Trigothysoid CHAcOBzS
125Trigonothyrin ABzAcBzMeT
126Trigonothyrin BHBzBzMeT
127Trigonothyrin CAcBzBzMeT
128Trigothysoid LAcBzAcPhT
129Trigonostempene BAcAcBzMeT
130Trigochinin COAcPhU
131Trigothysoid KOBzMeU
132Trigolins AHBzMeAcAcHBzV
133Trigolins BAcBzMeAcHHBzV
134Trigolins CAcBzMeAcBzHHV
135Trigolins DAcBzMeAcAcHBzV
136Trigolins EAcBzMeBzAcHAcV
137Trigolins FAcAcMeBzAcHBzV
138Trigolins GHBzMeBzACHBzV
139Trigothysoid HAcAcCH2OAcAcAcBzAcV
140Trigothysoid IAcAcCH2OAcAcAcHBzV
141Trigothysoid JAcBzMeAcAcHBzV
142Trigonosin DHHMeAcAcCOPhAcV
143Trigonothyrin DAcAcMeAcAcCOPhAcV
144Trigonothyrin EHAcMeAcAcCOPhAcV
145Trigochinin AHBzMeAcAcCOPhAcV
146Trigochinin BAcBzMeAcAcCOPhAcV
147Trigochinin DHBzMeAcAcBzAcV
148Trigochinin EAcBzMeAcAcBzAcV
149Trigochinin FAcAcAcAcAcBzAcV
150Trigonostempene AW
Table 5. Reported structures of 1-alkyldaphnanes skeletons.
Table 5. Reported structures of 1-alkyldaphnanes skeletons.
No.NameR1R2R3R4R5R6Type
151Stelleralide ACH2OAcOHOBzOHX1
152Stelleralide BCH2OBzHOBzOHX1
153GnidimacrinCH2OBzOHOBzOHX1
154Genkwadane BMeHOHOBzX1
155Pimelea factor P2CH2OHHOBzOHX1
156Genkwadane CHbenzoylHHMeX2
157Wikstroelide RHbenzoylOHHMeX2
158Wikstroelide SbenzoylHHMeHX2
159Wikstroelide THtrans-cinnamoylHHMeX2
160Kirkinine BHCH=CH(CH2)5MeHMeHX3
161Kirkinine CHCH=CH(CH2)5MeHMeOAcX3
162Kirkinine EHCH=CH(CH2)5MeOHMeHX3
163Wikstroelide EHCH2MeHMeHX3
164Wikstroelide FHCH2CH2OBzHMeHX3
165Wikstroelide Gpalmitic acidCH2CH2OBzHMeHX3
166Wikstroelide KCO(CH2)14CH3CH2CH2OBzMeHHX3
167Wikstroelide OHCH2CH2OBzMeHHX3
168Pimelea factor S6OHCH2MeHMeHX3
169Pimelea factor S7OHCH2MeMeHHX3
170Pimelotide AHHMeHX4
171Pimelotide BOAcHHMeX4
172Pimelotide CHHHMeX4
173Pimelotide DOAcHMeHX4
174Stelleralide CHOBzMeHX4
Table 6. Reported structures of rediocides skeletons.
Table 6. Reported structures of rediocides skeletons.
No.NameR1R2R3Type
175Trigochilide AY1
176Rediocide AMeCOCH2CH(CH3)2OHY2
177Rediocide CMeBzOHY2
178Rediocide EHCOCH2CH(CH3)2OHY2
179Rediocide FHBzOHY2
180Trigonosin EMeCOPhOHY2
181Trigonosin FMeCOPhOHY2
182Trigothysoid NMeCOCH2CH(CH3)2OHY2
183Trigothysoid OMeCOPhHY2
184Trigothysoid PMeCOCH2CH(CH3)2HY2
185Trigonostempene DMeValHY2
186Trigochilide BY3
187Rediocide BCOCH2CH(CH3)2Y4
188Rediocide GBzY4
189Rediocide DCOCH2CH(CH3)2Y5

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