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    Topic review

    Phytochemicals of the Genus Maytenus

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    Submitted by: yuanyuan huang

    Definition

    The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure.

    1. Introduction

    Plants of the genus Maytenus, a widely distributed member of the Celastraceae family, include approximately 300 plant species that are spread in tropical and subtropical regions of the world [1]. The genus Maytenus is widely used in folk medicines around the world, with the roots, bark and leaves being used for the treatment of cancer, gastric ulcers and arthritis because of their anti-inflammatory, analgesic, antiallergic and antitumor properties [2][3][4][5]. Studies have shown that a diverse group of chemical substances, triterpenoids, sesquiterpenes and alkaloids, are responsible for the various biological activities of the plants in this genus [6]. Among them, the macrolide alkaloid, maytansine, was first isolated from M. serrata [7], and was shown to be an anti-tumor agent with a novel structure, having some clinical potential. In a clinical trial, maytansine was shown to have promising anti-tumor activities against lymphocytic leukemia, lymphoma, ovarian cancer, breast cancer and melanomas [8][9]. Owing to its unique skeleton and remarkable bioactivity, maytansine has attracted a lot of interest for the possible reconstruction of its core structure. Many synthetic studies of the partial structure of maytansine have been reported. Furthermore, several friedelane triterpenoids with their aromatized characteristic structures and sesquiterpene pyridine alkaloids have been isolated from the genus Maytenus, and these have also showed good anti-tumor [10][11] and anti-bacterial [12] characteristics. The new chemical constituents and biological activities of Maytenus are given in this review of work from the past 45 years, as well as several chemical synthesis methods of maytansine or maytansine fragments, with the view of realizing their potential development and utilization in the medical field.

    2. Chemical Constituents of Maytenus

    Over the past decades, a large variety of biologically active secondary metabolites have been isolated and identified from the members of the genus Maytenus, which include a series of triterpenoids, such as friedelane triterpenoids, lupane triterpenes, oleanane triterpenes, sesquiterpenes and their alkaloids, along with some potent anti-tumor maytansinoids. Many scholars have extensively investigated the species, which belong to the genus Maytenus, and they have isolated several novel compounds with a wide variety of structures, which may prove to be useful against different diseases.

    2.1. Triterpenoids

    The genus Maytenus is a rich source of triterpenoids. These types of compounds are characteristic components found in this genus. The known triterpenoids from 1995 to 2005 were summarized by Zhang et al. [13] and Pu et al. [14][15]. Since then, several new triterpenoids have been discovered. Therefore, we have attempted to update all the data relating to the new triterpenoids isolated from the genus Maytenus from 1976 to 2021.

    2.1.1. Friedelane Friterpenoids

    Friedelane triterpenoids are important characteristic components of the Celastraceae family. Moreover, they are endowed with novel chemical diversity and possess a broad spectrum of biological activities. The friedelane triterpenoids are pentacyclic triterpenes composed of 30 carbons, which are converted from oleanolic acid by methyl shifts. In the five six-membered rings, the A/B, B/C and C/D rings are all trans and the D/E rings are mostly cis (i.e., H-18β). There is one β-CH3 substitution at each of the C-4, C-5, C-9, C-14 and C-17 positions. The C-3 position is often substituted with a hydroxyl group, although sometimes the hydroxyl group is oxidized to a carbonyl group.
    The compound pristimerin (1) was isolated from M. chuchuhuasca [16]. A new nortriterpene quinone methide, 15α-hydroxy-21-keto-pristimerine (2), has been obtained from the root bark of M. catingarum [17]. Fourteen compounds, including 2,3,22β-trihydroxy-24,29-dinor-1,3,5(10), 7-friedelatetraene-6,21-dione-23-al (3), 2,22β-dihydroxyl-3-methoxy-24,29-dinor-1,3,5(10), 7-friedelatetraene-6,21-dione (4), 2,3,22β-triihydroxy-23,24,29-trinor-1,3,5(10), 7-friedelatetr aene-6,21-dione (5), 2,22β-dihydroxyl-3-methoxy-24,29-dinor-1,3,5(10), 7-friedelatetraene-6,21-dione (6), 2,3,22β-trihydroxy-24,29-dinor-1,3,5(10)-friedelatetraene-6,21-dione (7), 2,15α,22β-trihydroxy-3-methoxy-24,29-dinor-1,3,5(10)-friedelatriene-21-one (8), 3,22β-dihydroxy-24,29-dinor-l(10)-3,5-friedelatriene-2,7,21-trione (9), 3,22β-dihydroxy-24,29-dinor-l(10), 3,5-friedelatriene-21-one (10), 2,3,22β-trihydroxy-24,29-dinor-25(9→8)-1,3,5(10), 7-friedelatetraene-21-one-23-al (11), 23-oxo-iso-tingenone (12), (8S)-7,8-dihydro-7-oxo-tingenoe (13), (7S,8S)-7-hydroxy-7,8-dihydro-tingenone (14), (8S)-7,8-dihydro-6-oxo-tingenol (15) and 23-nor-6-oxo-tingenol (16) were isolated from the roots of M. amazonica [18][19]. Compounds 28-hydroxy-friedelane-1,3-dione (17) and macrocarpins A–D (1821) were obtained from the roots of M. macrocarpa [20][21], while maytenfolone (22) has been isolated from M. diversifolia [22]. Three compounds 6-oxo-iguesterol (23), 6-oxo-tingenol (24) and 3-O-methoxy-6-oxo-tingenol (25) have been obtained from the root bark of M. canariensis [12]. Four new triterpenes blepharotriol (26), 6-deoxoblepharodol (27), isoblepharodol (28) and 7-oxo-blepharodol (29) were separated from M. blepharodes [23].
    Compounds 15α-hydroxy-tingenone (30), 15-dehydro-pristimerin (31), vitideasin (32) and 20β-hydroxy-scutione (33) were separated from the roots of M. vitis-idaea [24]. Six new compounds, including 7-oxo-7, 8-dihydro-scutione (34), 6,23-dioxo-7,8-dihydro-pristimerol-23-oic Acid (35), 23-nor-blepharodol (36), 3-methoxy-6-oxo-tingenol-23-oic Acid (37), retusonine (38) and 21-Oxopristimerine (39) were isolated from the root bark of M. retusa [25]. A new compound 3-O-Methyl-6-oxo-pristimerol (40) has been isolated from the hexane/Et2O 1:1 extract of the root bark of M. chubutensis [26]. Compounds 3β,24-epoxy-2α,3α-dihydroxy-D:A-friedooleanan-29-oic acid methyl ester (41), 2α-acetoxy-3β,24-epoxy-3α-hydroxy-D:A-friedooleanan-29-oic acid methyl ester (42), 3α-hydroxy-D:A-friedooleanan-28-oic acid (43) and 3-oxo-D:A-friedooleanan-28,30-olide (44) were obtained from the root bark of M. jelskii [27]. Compounds 3β,11β-dihydroxyfriedelane (45) and 3,4-seco-friedelan-3,11β-olide (46) have been obtained from the hexane extracts of the leaves of M. robusta [28], while (16β)-16-hydroxy-pristimerin (47) was from M. salicifolia [29]. A new triterpenoid, 12,16-dihydroxyfriedelan-3-one (48), was isolated from an ethyl acetate extract of M. oblongata [30]. Compounds 3β,24β-epoxy-29-methoxy-2α,3α,6α-trihydroxy-D:A-friedelane (49) and 3β,24β-epoxy-29-methoxy-2α,3α,6α-triacetoxy-D:A-friedelane (49a) were obtained from the root bark extracts of M. cuzcoina [31]. Three new pentacyclic triterpenoids, friedel-1-en-3,16-dione (50), 1α,29-dihydroxyfriedelan-3-one (51) and 16β,28,29-trihydroxyfriedelan-3-one (52) have been separated from M. robusta [32]. Dispemroquinone (53) was isolated from M. dispermus [33]. A new norquinonemethide triterpene with a netzahualcoyene type skeleton, scutione (54), was isolated from the root bark of M. scutioides [34]. Compounds zeylasterone (55) and demethylzeylasterone (56) were obtained from M. blepharodes [35], and compound 3,15-dioxo-21α-hydroxy friedelane (57) was isolated from the methanol extracts of M. robusta [36]. Maytenfoliol (58) was separated from M. diversifolium [37]. Four new cytotoxic triterpenoid dimers, including cangorosin A (59), atropcangorosin A (60), dihydroatropcangorosin A (61) and cangorosin B (62) were obtained from the extracts of M. ilicifolia [38]. Two new triterpenes, umbellatin α (63) and umbeilatin β (64), have been separated from M. umbellata [39]. Two novel trimer triscutins, A and B (6566), have been isolated from extracts of the root bark of M. scutioides [40]. Four new triterpene dimers, xuxuarine Eα (67), scutionin αB (68), 6′,7′-dihydro-scutionin αB (69) and 6′β-methoxy-6′,7′dihydro-scutionin αB (70), have been isolated from the extracts of the roots of M. blepharodes and M. magellanica [41][42] (Table 1 and Figure 1).
    Figure 1. Twenty-five types (A1–A25) of friedelane triterpenoids skeletons.
    Table 1. The friedelane triterpenes isolated from Maytenus.
    No. Name R1 R2 R3 R4 R5 R6 R7 R8 Type Ref.
    1 Pristimerin H H COOMe H H - - - A1 [16]
    2 15α-hydroxy-21-keto-pristimerine α-OH H COOMe =O H - - - A1 [17]
    3 2,3,22β-trihydroxy-24,29-dinor-1,3,5(10),7-friedelatetraene-6,21-dione-23-al OH OH CHO H =O β-OH - - A2 [18]
    4 2,22β-dihydroxyl-3-methoxy-24,29-dinor-1,3,5(10),7-friedelatetraene-6,21-dione OH OH CH3 H =O β-OH - - A2 [18]
    5 2,3,22β-triihydroxy-23,24,29-trinor-1,3,5(10),7-friedelatetr aene-6,21-dione OH OH H H =O β-OH - - A2 [18]
    6 2,22β-dihydroxyl-3-methoxy-24,29-dinor-1,3,5(10),7-friedelatetraene-6,21-dione OH OCH3 CH3 H =O β-OH - - A2 [18]
    7 2,3,22β-trihydroxy-24,29-dinor-1,3,5(10)–friedelatetraene -6,21-dione OH CH3 =O H H H =O β-OH A3 [18]
    8 2,15α,22β-trihydroxy-3-methoxy-24,29-dinor-1,3, 5(10)-friedelatriene-21-one OCH3 CH3 H H α-OH H =O β-OH A3 [18]
    9 3,22β-dihydroxy-24,29-dinor-l(10)-3,5-friedelatriene-2,7,21-trione =O β-OH =O H - - - - A4 [18]
    10 3,22β-dihydroxy-24,29-dinor-l(10),3,5–friedelatriene-21-one H β-OH =O H - - - - A4 [18]
    11 2,3,22β-trihydroxy-24,29-dinor-25(9→8)-1,3,5(10),7-friedelatetraene-21-one-23-al β-OH - - - - - - - A5 [18]
    12 23-oxo-iso-tingenone H - - - - - - - A5 [19]
    13 (8S)-7,8-dihydro-7-oxo-tingenoe =O H =O H - - - - A4 [19]
    14 (7S, 8S)-7-hydroxy-7,8-dihydro-tingenone α-OH H =O H - - - - A4 [19]
    15 (8S)-7,8-dihydro-6-oxo-tingenol OH CH3 =O H H H =O H A3 [19]
    16 23-nor-6-oxo-tingenol OH OH H H =O H - - A2 [19]
    17 28-hydroxy-friedelane-1,3-dione =O H H H CH2OH CH3 CH3 - A6 [20]
    18 Macrocarpin A OH CHO =O H H COOMe H H A3 [21]
    19 Macrocarpin B OH OH COOH H =O β-OH - - A2 [21]
    20 Macrocarpin C OH OCH3 COOH H =O β-OH - - A2 [21]
    21 Macrocarpin D α-OH β-OH =O H - - - - A4 [21]
    22 Maytenfolone - - - - - - - - A7 [22]
    23 6-oxo-iguesterol - - - - - - - - A8 [12]
    24 6-oxo-tingenol OH OH CH3 H =O H - - A2 [12]
    25 3-O-methoxy-6-oxo-tingenol OH OCH3 CH3 H =O H - - A2 [12]
    26 Blepharotriol OH OH OH COOMe H H - - A2 [23]
    27 6-deoxoblepharodol OH CH3 H H H COOMe H H A3 [23]
    28 Isoblepharodol OH CH3 H =O H COOMe H H A3 [23]
    29 7-oxo-blepharodol OH CH3 =O =O H COOMe H H A3 [23]
    30 15α-hydroxy-tingenone α-OH H H =O H - - - A1 [24]
    31 15-dihydro-pristimerin - - - - - - - - A9 [24]
    32 Vitideasin α-COOCH3 H - - - - - - A10 [24]
    33 20β-hydroxy-scutione α-OH =O - - - - - - A10 [24]
    34 7-oxo-7,8-dihydro-scutione - - - - - - - - A11 [25]
    35 6,23-dioxo-7,8-dihydro-pristimerol-23-oic Acid OH COOH =O H H COOMe H H A3 [25]
    36 23-nor-blepharodol OH H =O H H COOMe H H A3 [25]
    37 3-methoxy-6-oxo-tingenol-23-oic Acid OH OCH3 COOH H =O H - - A2 [25]
    38 Retusonine - - - - - - - - A12 [25]
    39 21-Oxopristimerine H H COOMe =O H - - - A1 [25]
    40 3-O-methyl-6-oxo-pristimerol OH OCH3 CH3 COOMe H H - - A2 [26]
    41 3β,24-epoxy-2α,3α-dihydroxy-D:A-friedooleanan-29-oic acid methyl ester OH OH H - - - - - A13 [27]
    42 2α-acetoxy-3β,24-epoxy-3α-hydroxy- D:A-friedooleanan-29-oic acid methyl ester OAc OH H - - - - - A13 [27]
    43 3α-hydroxy- D:A-friedooleanan-28-oic acid α-OH H H COOH H - - - A14 [27]
    44 3-oxo-D:A-friedooleanan-28,30-olide - - - - - - - - A15 [27]
    45 3β,11β-dihydroxyfriedelane β-OH β-OH H CH3 H - - - A14 [28]
    46 3,4-seco-friedelan-3,11β-olide - - - - - - - - A16 [28]
    47 (16β)-16-hydroxy-pristimerin H β-OH COOMe H H - - - A1 [29]
    48 12,16-dihydroxyfriedelan-3-one H H α-OH β-OH CH3 CH3 CH3 - A6 [30]
    49 3β,24β-epoxy-29-methoxy-2α,3α,6α-trihydroxy-D:A-friedelane OH OH β-OH - - - - - A13 [31]
    49a 3β,24β-epoxy-29-methoxy-2α,3α,6α-triacetoxy-D:A-friedelane OAc OAc β-OAc - - - - - A13 [31]
    50 Friedel-1-en-3,16-dione - - - - - - - - A17 [32]
    51 1α,29-dihydroxyfriedelan-3-one α-OH H H H CH3 CH3 CH2OH - A6 [32]
    52 16β,28,29-trihydroxyfriedelan-3-one H H H β-OH CH2OH CH3 CH2OH - A6 [32]
    53 Dispemroquinone =O H H COOMe - - - - A5 [33]
    54 Scutione H =O - - - - - - A10 [34]
    55 Zeylasterone OH OH COOH COOMe H H - - A2 [35]
    56 Demethylzeylasterone OH OH COOH COOH H H - - A2 [35]
    57 3,15-dioxo-21-hydroxy friedelane =O H =O CH3 α-OH - - - A14 [36]
    58 Maytenfoliol H H H H CH2OH CH2OH CH3 - A6 [37]
    59 Cangorosin A H - - - - - - - A18 [38]
    60 Atropcangorosin A H(atropisomer of 7-bu) - - - - - - - A18 [38]
    61 Dihydroatropcangorosin A 6′,7′-dihydro derivative of 8-BU - - - - - - - A18 [38]
    62 Cangorosin B - - - - - - - - A19 [38]
    63 Umbellatin α α-Me - - - - - - - A20 [39]
    64 Umbeilatin β β-Me - - - - - - - A20 [39]
    65 Tiscutin A - - - - - - - - A21 [40]
    66 Triscutin B - - - - - - - - A22 [40]
    67 Xuxuarine Eα - - - - - - - - A23 [41]
    68 Scutionin αB - - - - - - - - A24 [42]
    69 6′,7′-dihydro-scutionin αB H - - - - - - - A25 [42]
    70 6′β-methoxy-6′,7′dihydro-scutionin αB OCH3 - - - - - - - A25 [42]

    2.1.2. Lupane Triterpenes

    Lupane triterpenes are characterized by the combination of C-21 and C-19, clustered into a five-membered carbocyclic E ring. There is an isopropyl group substituted at the 19th position of the E ring with an α configuration, as well as a double bond at the C-20(29) position. The rings of the A/B, B/C, C/D and D/E types are all trans. The new triterpenes 3β,28,30-Lup-20(29)-ene triol (71) and 28,30-Dihyroxylup-20(29)-ene-3-one (72) were obtained from M. canariensis [43], while compound maytefolin A (73) was isolated from the leaves of a Brazilian medicinal plant, M. ilicifolia [44]. 3-oxo-lup-20(29)-en-30-al (74), 30-hydroxylup-20(29)-en-3-one (75), (11α)-11-hydroxylup-20(29)-en-3-one (76) and (3β)-lup-20(30)-ene-3,29-diol (77) have been obtained from the hexane extracts of the stems and branches of M. imbricate [45]. Compounds 11α-hydroxy-epi-betuin (78), 6β-hydroxybetulin (79), 24-hydroxybetulin (80), rigidenol-28-aldehyde (81) and 28-hydroxyglochidone (82) have been isolated from M. cuzcoina and M. chiapensis [46]. Compounds 11α-hydroxy-glochidone (83), 3-epi-nepeticin (84) and 3-epi-calenduladiol (85) were separated from the root barks of M. cuzcoina and the leaves of M. chiapensis [47]. Four new triterpenes, including 3α,16β,28-Trihydroxylup-20(29)-ene (86), 3α,16β-dihydroxylup-12-ene (87), 3β,16β-dihydroxylup-12-ene (88) and 16β-3,4-Secolup-20(29)-en-3-oic acid (89), were obtained from the aerial parts of M. apurimacensis [48], while compound 3-(E)-β-coumaroylnepeticin (90) was isolated from M. retusa [25]. Compound 3,4-seco-lupa-4(23): 20(29)-diene-3,28-dioic acid 28-methyl ester (91) has been separated from the hexane/Et2O 1:1 extracts of the root barks of M. magellanica [26]. 1β-Hydroxy-3β-caffeate lup-20(29)-ene (92) was isolated from the roots of M. apurimacensis [49]. Compounds 3-oxo-21β-H-hop-22(29)-ene (93), 3β-hydroxy-21β-H-hop-22(29)-ene (94) and 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (95) were isolated from the leaves of M. robusta [28] (Table 2 and Figure 2).
    Figure 2. Seven types (B1–B7) of lupane triterpenes skeletons.
    Table 2. The lupane triterpenes isolated from Maytenus.
    No. Name R1 R2 R3 R4 R5 R6 R7 R8 R9 Type Ref
    71 3β,28,30-Lup-20(29)-ene triol H H OH CH3 H H H CH2OH CH2OH B1 [43]
    72 28,30-Dihyroxylup-20(29)-ene-3-one H H =O CH3 H H H CH2OH CH2OH B1 [43]
    73 Maytefolins A H α-OH =O CH3 H H H CH2OH CH3 B1 [44]
    74 3-oxolup-20(29)-en-30-al H H =O CH3 H H H CH3 CHO B1 [45]
    75 30-hydroxylup-20(29)-en-3-one H H =O CH3 H H H CH3 CH2OH B1 [45]
    76 (11α)-11-hydroxylup-20(29)-en-3-one H H =O CH3 H α-OH H CH3 CH3 B1 [45]
    77 (3β)-lup-20(30)-ene-3,29-diol H H β-OH CH3 H H H CH3 CH2OH B1 [45]
    78 11α-hydroxy-epi-betuin H H α-OH CH3 H α-OH H CH2OH CH3 B1 [46]
    79 6β-hydroxybetulin H H β-OH CH3 β-OH H H CH2OH CH3 B1 [46]
    80 24-hydroxybetulin H H =O CH2OH H H H CH2OH CH3 B1 [46]
    81 Rigidenol-28-aldehyde H H =O CH3 H α-OH H CHO CH3 B1 [46]
    82 28-hydroxyglochidone H CH2OH - - - - - - - B2 [46]
    83 11α-hydroxy-glochidone α-OH CH3 - - - - - - - B2 [47]
    84 3-epi-nepeticin H H α-OH CH3 H α-OH H CH3 CH3 B1 [47]
    85 3-epi-calenduladiol H H α-OH CH3 H H H OH CH3 B1 [47]
    86 3α,16β,28-Trihydroxylup-20(29)-ene H H α-OH CH3 H H β-OH CH2OH CH3 B1 [48]
    87 3α,16β-dihydroxylup-12-ene α-OH β-OH - - - - - - - B3 [48]
    88 3β,16β-dihydroxylup-12-ene β-OH β-OH - - - - - - - B3 [48]
    89 16β-3,4-secolup-20(29)-en-3-oic acid - - - - - - - - - B4 [48]
    90 3-(E)-β-coumaroylnepeticin H H Molecules 26 04563 i001 CH3 H α-OH H CH3 CH3 B1 [25]
    91 3,4-seco-lupa-4(23):20(29)-diene-3,28-dioicacid 28-methyl ester - - - - - - - - - B5 [26]
    92 1β-Hydroxy-3β-caffeate lup-20(29)-ene β-OH H OCaf CH3 H H H CH3 CH3 B1 [49]
    93 3-oxo-21β-H-hop-22(29)-ene =O - - - - - - - - B6 [28]
    94 3β-hydroxy-21β-H-hop-22(29)-ene β-OH - - - - - - - - B6 [28]
    95 3,4-seco-21β-H-hop-22(29)-en-3-oic acid - - - - - - - - - B7 [28]

    2.1.3. Oleanane Triterpenes

    Oleanane triterpenes are widely distributed in the plant kingdom. The configuration of the rings is A/B, B/C and C/D, and they are all of the trans configuration, while the D/E ring is cis. There are eight methyl groups on the core nuclei, and the methyl groups at positions C-10, C-8 and C-17 are all β configuration. The methyl group at the C-14 position is α configuration, while the C-4 and C-20 positions each have two methyl groups. There may also be other substituents present in the molecule. Two new oleanane triterpenes, 3β,19α-dihydroxyolean-12-en-29-oic acid (96) and 3α,19α-dihydroxyolean-12-en-29-oic acid (97), were obtained from M. austyoyunnanensis [14]. Compound 3-oxo-11α-methoxyolean-12-ene (98) was obtained from the extracts of the roots of M. spinosa [24], while 22α-hydroxy-29-methoxy-3β-tetradecanoate-olean-12-ene (99) was separated from the root bark extracts of M. cuzcoina [31]. The new compound maytefolin B (100) was separated from the leaves of a Brazilian medicinal plant, M. ilicifolia [44]. One new triterpene, 3β-peroxy-7β,25-epoxy-D:B-friedoolean-5-ene (101), was separated from the aerial parts of M. apurimacensis [48]. Compounds krukovines A (28-hydroxyolean-12-ene-3,11-dione) (102) and krukovines C (6β,28-dihydroxyolean-12-ene-3,11-dione) (103) have been obtained from a South American medicinal plant known as “chuchuhuasi” (M. krukovii) [50]. The aerial parts of M. undata yielded four new 12-oleanene and 3,4-seco-12-oleanene triterpene acids, namely, 3-oxo-11α-methoxyolean-12-ene-30-oic acid (104), 3-oxo-11α-hydroxyolean-12-ene-30-oic acid (105), 3-oxo-olean-9(11), 12-diene-30-oic acid (106) and 3,4-seco-olean-4(23), 12-diene-3,29-dioic acid (107) [51], while 3α-22β-dihydroxyolean-12-en-29-oicacid (108) was obtained from the methanol extracts of the barks of M. laevis [52]. Compound olean-9(11):12-dien-3β-ol (109) was isolated from the roots of M. acanthophylla [53] and compound 3β-hydroxy-D:B-friedo-olean-5-ene (110) was isolated from M. salicifolia Reissek [54]. Compound 19α-hydroxy-3-olean-12-en-29-oic acid (111) was isolated from M. austyoyunnanensis [55] (Table 3 and Figure 3).
    Figure 3. Six types (C1–C6) of oleanane triterpenes skeletons.
    Table 3. The oleanane triterpenes isolated from Maytenus.
    No. Name R1 R2 R3 R4 R5 R6 R7 R8 Type Ref.
    96 3β,19α-dihydroxyolean-12-en-29-oic acid β-OH H H CH3 H α-OH CH3 COOH C1 [14]
    97 3α,19α-dihydroxyolean-12-en-29-oic acid α-OH H H CH3 H α-OH CH3 COOH C1 [14]
    98 3-oxo-11α-methoxyolean-12-ene =O H α-OCH3 CH3 H H CH3 CH3 C1 [24]
    99 22α-hydroxy-29-methoxy-3β-tetradecanoate-olean-12-ene β-COOC13H27 H H CH3 α-OH H CH3 COOMe C1 [31]
    100 Maytefolin B - - - - - - - - C2 [44]
    101 3β-peroxy-7β,25-epoxy-D:B-friedoolean-5-ene - - - - - - - - C3 [48]
    102 28-hydroxyolean-12-ene-3,11-dione =O H =O CH2OH H H CH3 CH3 C1 [50]
    103 6β,28-dihydroxyolean-12-ene-3,11-dione =O β-OH =O CH2OH H H CH3 CH3 C1 [50]
    104 3-oxo-11α-methoxyolean-12-ene-30-oic acid =O H α-OCH3 CH3 H H COOH CH3 C1 [51]
    105 3-oxo-11α-hydroxyolean-12-ene-30-oic acid =O H α-OH CH3 H H COOH CH3 C1 [51]
    106 3-oxo-olean-9(11),12-diene-30-oic acid =O COOH - - - - - - C4 [51]
    107 3,4-seco-olean-4(23),12-diene-3,29-dioic acid - - - - - - - - C5 [51]
    108 3α-22β-dihydroxyolean-12-en-29-oicacid α-OH H H CH3 β-OH H CH3 COOH C1 [52]
    109 Olean-9 (11):12-dien-3β-ol β-OH CH3 - - - - - - C4 [53]
    110 3β-Hydroxy-D:B-friedo-olean-5-ene - - - - - - - - C6 [54]
    111 19α-hydroxy-3-olean-12-en-29-oic acid =O H H CH3 H α-OH CH3 COOH C1 [55]

    2.1.4. Other Triterpenes

    In addition to the above, other types of triterpene compounds have also been isolated from Maytenus. These include triterpene dimers, ursane triterpenes and dammarane triterpenes. The compound 3-Oxo-methoxyurs-12-ene (112) was isolated from M. spinosa [24]. Three ursane triterpenes, krukovines B, D and E (113115), were obtained from M. krukovii [50]. Compound maytefolin C (116) has been isolated from the leaves of M. ilicifolia [44], while 28-hydroxy-12-ursene-3β-yl-caffeate (uvaol-3-caffeate) (117) has been isolated from the methanol extracts of the barks of M. laevis [52]. An ursane triterpene 3β-stearyloxy-urs-12-ene (118) was obtained from M. salicifolia [56]. The stem bark exudates of M. macrocarpa yielded ten dammarane triterpenes, namely, 24-(E)-3-oxo-dammara-20,24-dien-26-al (119), 24-(Z)-3-oxo-dammara-20,24-dien-26-al (120), 24-(E)-3-oxo-dammara-20,24-dien-26-ol (121), 24-(E)-3-oxo-dammara-23-α-hydroxy-20,24-dien-26-al (122), 24-(E)-3-oxo-dammara-23-β-hydroxy-20,24-dien-26-al (123), 24-(E)-3-oxo-dammara-6-β-hydroxy-20, 24-dien-26-al (124), 24-(E)-3-oxo-dammara-6-β-hydroxy-20,24-dien-26-ol (125), 23-(Z)-3, 25-dioxo-25-nor-dammara-20,24-diene (126), 24-(E)-3-oxo-23-methylene-dammara-20,24-dien-26-oico (127), 24(Z)-3-oxodammara20(21),24-dien-27-oic acid (128) and octa-nor-13-hydroxydammara-1-en-3,17-dione (129). This was in 1997, and it was the first time that dammrane triterpenes were isolated from Celastraceae [57][58] (Table 4 and Figure 4).
    Figure 4. Seven types (D1–D7) of other triterpenes skeletons.
    Table 4. The other triterpenes isolated from Maytenus.
    No. Name R1 R2 R3 R4 Type Ref.
    112 3-Oxo-methoxyurs-12-ene =O H α-OCH3 CH3 D1 [24]
    113 Krukovines B =O H CH2OH H D1 [50]
    114 Krukovines D =O OH CH2OH H D1 [50]
    115 Krukovines E =O H OH H D1 [50]
    116 Maytefolins C - - - - D2 [44]
    117 28-hydroxy-12-ursene-3β-yl-caffeate β-OCaf H CH2OH H D1 [52]
    118 3β-stearyloxy-urs-12-ene Molecules 26 04563 i002 H CH3 H D1 [56]
    119 24-(E)-3-oxo-dammara-20,24-dien-26-al - - - - D3 [57]
    120 24-(Z)-3-oxo-dammara-20,24-dien-26-al - - - - D3 [57]
    121 24-(E)-3-oxo-dammara-20,24-dien-26-ol H H CH3 CH2OH D4 [57]
    122 24-(E)-3-oxo-dammara-23-α-hydroxy-20,24-dien-26-al H α-OH CH3 CHO D4 [57]
    123 24-(E)-3-oxo-dammara-23-β-hydroxy-20,24-dien-26-al H β-OH CH3 CHO D4 [57]
    124 24-(E)-3-oxo-dammara-6-β-hydroxy-20,24-dien-26-al β-OH H CH3 CHO D4 [57]
    125 24-(E)-3-oxo-dammara-6-β-hydroxy-20,24-dien-26-ol β-OH H CH3 CH2OH D4 [57]
    126 23-(Z)-3,25-dioxo-25-nor-dammara-20,24-diene - - - - D5 [57]
    127 24-(E)-3-oxo-23-methylene-dammara-20,24-dien-26-oico - - - - D6 [58]
    128 24(Z)-3-oxodammara20(21),24-dien-27-oic acid H H COOH CH3 D4 [58]
    129 Octa-nor-13-hydroxydammara-1-en-3,17-dione - - - - D7 [58]

    2.2. Sesqiterpenoids

    The most widespread and characteristic metabolites isolated from the Celastraceae family are a large group of unusual and highly oxygenated sesquiterpenoids, based on the [5,11-epoxy-5β,10α-eduesman-4(14)-ene] skeleton known as dihydro-β-agarofum. Sesquiterpenes have multiple substitution sites in their structure, and common substituents include -OH, -OAc, -Ofu, -Obz and -Onic, which is due to the diversification of their positions and types. There is a high probability that there are several new compounds from this group that still need to be discovered [59].
    Two sesquiterpene polyesters with new polyhydroxy skeletons, 1α,9α-dibenzoyloxy-6β,8α,15-triacetoxy-4β-hydroxy-dihydro-β-agarofurane (130) and 1α,9α-dibenzoyloxy-2α,6β,8α,15-tetracetoxy-4β-hydroxydihydro-β-agrofurane (131), were isolated from the aerial portions of M. canariensis [60]. Compounds 6β,8β-15-triacetoxy-1α,9α-dibenzoyloxy-4β-hydroxy-β-dihydroagarofuran (132), 1α,6β,8β,15-tetraacetoxy-9α-benzoyloxy-4β-hydroxy-β-dihydroagarofuran (133) and (1S,4S,6R,7R,8R,9R)-1,6,15-triacetoxy-8,9-dibenzoyloxy-4β-hydroxy-β-dihydroagarofuran (134) were isolated from the aerial parts of M. macrocarpa [61]. Compounds (1R,2S,4S,5S,6R,7R,9S,10S)-6,15-diacetoxy-1,2,9-tribenzoyloxy-4-hrdroxy-8-oxo-dihydro-β-agarofuran (135) and 9β-cinnamoyloxy-2β,3β-diacetoxy-6β-hydroxy-lα-nicotinoyloxydihidro-β-agarofuran (136) were separated from M. blepharodes [41]. Eight sesquiterpenoids, including 1α-acetoxy-2α,6β,9β-trtifuroyloxy-4β-hydroxy-dihydro-β-agarofuran (137), 1α,2α-diacetoxy-6β,9β-difuroyloxy-4β-hydroxy-dihydro-β-agarofuran (138), 1α-acetoxy-6β,9β-difuroyloxy-2α,4β-dihydroxy-dihydro-β-agarofuran (139), 1α-acetoxy-2α-benzoyloxy-6β,9β-difuroyloxy-4β-dihydro-β-agarofuran (140), 1α-acetoxy-6β,9β-difuroyloxy-2α-propyonyloxy-4β-hydroxy-dihydro-β-agarofuran (141), 1α-acetoxy-6α,9β-difuroyloxy-2α-(2)-methylbutyroyloxy-4β-hydroxy-dihydro-β-agarofuran (142), 1α,2α,15-triacetoxy-6β,9β-difuroyloxy-4β-hydroxy-dihydro-β-agarofuran (143) and 1α,2α,15-triacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran (144) were obtained from the n-hexane: Et2O (1:1) extracts of the fruits of M. cuzcoina [59].
    The n-hexane/Et2O (1:1) extracts of the root barks of M. magellanica yielded eight new dihydro-β-agarofuran sesquiterpenes (145152), and the n-hexane/Et2O (1:1) extracts of the root barks of M. chubutensis yielded two more new compounds of this family (153154). Their structures were elucidated as (1R,2R,4S,5R,7S,9S,10R)-2-acetoxy-1-benzoyloxy-9-cinnamoyloxy-4-hydroxy-dihydro-β-agarofuran (145), (1R,2S,3S,5R,7R,9S,10R)-2-acetoxy-9-benzoyloxy-1-cinnamoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran (146), (1R,2S,3S,4S,5S,6R,7R,9S,10R)-2,6-diacetoxy-1-benzoyloxy-9-cinnamoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran (147), (1R,2S,3S,4S,5S,6R,7R,9S,10R)-2,6-diacetoxy-1,9-dibenzoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran (148), (1R,2S,3S,4S,5R,7S,8S,9R,10R)-2,3-diacetoxy-8,9-dibenzoyloxy-1-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran (149), (1R,2S,4S,5S,6R,7R,8S,9R,10S)-6,8-diacetoxy-1,2,9-tribenzoyloxy-4-hydroxy-dihydro-β-agarofuran (150), (1R,2S,3S,4S,5R,7S,8S,9R,10R)-2,8-diacetoxy-3,9-dibenzoyloxy-1-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran (151), (1R, 2S,4R,5S,6R,7R,8S,9R,10S)-6,8-diacetoxy-1,9-dibenzoyloxy-2-nicotinoyloxy-dihydro-β-agarofuran (152), 1α,15-diacetoxy-6β,9β-dibenzoyloxy-2α-nicotinoyloxy-dihydro-β-agarofuran (153) and 1α,15-diacetoxy-6β,9β-dibenzoyloxy-2α-nicotinoyloxy-4β-hydroxy-dihydro-β-agarofuran (154) [62]. Compounds (1R,2S,4S,5S,6R,7R,9S,10S)-1,2,6,9,15-pentaacetoxy-4-hydroxy-8-oxo-dihydro-β-agarofuran (155), (1R,2S,4S,5S,6R,7R,9S,10S)-1,2,9,15-taacetoxy-4,6-dihydroxy-8-oxo-dihydro-β-agarofuran (156), (1R,2S,4S,5S,6R,7R,9S,10S)-1,9,15-triacetoxy-2,4,6-trihydroxy-8-oxo-dihydro-β-agarofuran (157), (1R,2S,3S,4S,5S,6R,7R,9S,10S)-1,2,3,6,9,12,15-heptaacetoxy-4-hydroxy-8-oxo-dihydro-β-agarofuran (158) and 1α,2α,3β,6β,8α,9α,12,15-octaacetoxy-4β-hydroxy-dihydro-β-agarofuran (159) were isolated from the leaves of M. chiapensis [63]. In addition, (1S,4S,5S,6R,7R,8S,9R,10R)-8-acetoxy-1,9-dibenzoyloxy-6-nicotynoyloxy-dihydro-β-agarofuran (160) and (1S,4R,5R,6R,7R,8S,9R,10R)-8-acetoxy-1,9-dibenzoyloxy-4-hydroxy-nicotynoyloxy-dihydro-β-agarofuran (161) have been isolated from the roots of M. apurimacensis [49].
    Thirteen sesquiterpenes, including (1R,2S,4S,5S,6R,7R,9S,10R)-115-diacetoxy-2,6-dibenzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (162), (1R,2S,4S,5S,6R,7R,9S,10R)-1,2,15-triacetoxy-6-benzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (163), (1R,2S,4S,5S,6R,7R,9S,10R)-1,15-diacetoxy-6-benzoyloxy-9-(3-furoyloxy)-2,4-dihydroxy-dihydro-β-agarofuran (164), (1R,2S,4S,5S,6R,7R,9S,10R)-1,15-diacetoxy-6,9-dibenzoyloxy-2,4-hydroxy-dihydro-β-agarofuran (165), (1R,2S,4S,5S,6R,7R,9S,10R)-1,2,6,15-tetracetoxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (166), (1R,2S,4S,5S,6R,7R,9S,10R)-1-Acetoxy-2,6-dibenzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (167), (1S,2S,3S,4S,5R,7R,9S,10R)-2,3-diacetoxy-9-benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (168), (1S,2R,4S,5R,7R,9S,10R)-2-acetoxy-9-benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (169), (1S,2R,4S,5R,7R,9S,10R)-2-Acetoxy-1,9-di-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (170), (1S,2R,4S,5R,7R,9S,10R)-2-Acetoxy-9-trans-cynamoiloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (171), (1S,4S,5R,7R,9S,10S)-9-Benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran (172), (1S,2R,3R,4R,5S,7R,9S,10R)-2,3-diacetoxy-9-benzoyloxy-1-(3-furoyloxy)-dihydro-β-agarofuran (173) and (1S,2R,4R,5S,7R,9S,10R)-2-Acetoxy-9-benzoyloxy-1-(3-furoyloxy)-dihydro-β-agarofuran (174) have been isolated from the hexanee-Et2O extracts of the fruits of M. jelskii [64]. Nine new β-dihydroagarofurans, 1α2α,9β,15-tetracetoxy-8β-benzoyloxy-β-dihydroagarofuran (175), 1α-benzoyloxy-2α,6β,8α-triacetoxy-9α-methyllbutyroyloxy-β-dihydroagarofuran (176), 1α,6β-diacetoxy-2α,8α,9α-tribenzoyloxy-β-dihydroagarofuran (177), 1α-benzoyloxy-2α,6β,8α,9α-tetraacetoxy-β-dihydroagarofuran (178), 1α,6β,8α-triacetoxy-9α-benzoyloxy-2α-hydroxy-β-dihydroagarofuran (179), (1R,2S,4R,5S,6R,7R,8R,9S,10S)-1,6-diacetoxy-8,9-dibenzoyloxy-2-h ydroxy-β-dihydroagarofuran (180), 1α,6β,15-triacetoxy-8α-methylbutyroyloxy-9α-benzoyloxy-2α-hydroxy-β-dihydroagaro-furan (181), 1α,6β,15-triacetoxy-8α,9α-dibenzoyloxy-2α-hydroxy-β-dihydroagarofuran (182) and 1α,6β,8β,15-tetracetoxy-2α-hydroxy-9α-benzoyloxy-β-dihydroagarofuran (183), were isolated from the leaves of M. spinosa [65]. Five new compounds, chiapens A–E (184188), were isolated from M. chiapensis [66].
    Compounds 1α,6β-diacetoxy-8α-hydroxy-9β-furoyloxy-β-agarofuran (189), 1α-acetoxy-6β,8α-dihydroxy-9β-furoyloxy-β-agarofuran (190), 1α-benzoyloxy-2α,3β,6β,9β,14-pentaacetoxy-8-oxo-β-agarofuan (191) and 1α-furoyloxy-2α,3β,6β,9β,14-pentaacetoxy-8-oxo-β-agarofuan (192) were obtained from an extract of the seeds of M. boaria [67]. Bilocularins A−I (193201) were isolated from M. bilocularis. In addition, bilocularins D–F are the first examples of dihydro-b-agarofurans, which bear a hydroxyacetate group [68][69]. Compounds (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9,10-trihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate (202), (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate) (203), (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5, 10-diyl bis(furan-3-carboxylate) (204) and (1S,4S,5S,6R,7R,9S, 10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]-oxepin-5-yl furan-3-carboxylate (205) were isolated from the seeds of M. boaria [70][71]. Compounds 2β,6β-diacetoxy-1α,9β-dibenzoyl-3β-hydroxy-dihydro-β-agarofuran (206), 1α,2α,6β,8α-tetraacetoxy-9β-benzoyl-15-hydroxy-dihydro-β-agarofuran (207) and 1α,2α,6β,8α,15-pentaacetoxy-9β-benzoyl-dihydro-β-agarofuran (208) have been separated from M. boaria [72]. 1β-acetoxy-9α-benzoyloxy-2β,6α-dinicotinoyloxy-β-dihydroagarofuran (209) was obtained from the anti-microbially active ethanol extracts of M. heterophylla [73]. In addition, an eudesmane glucoside, boarioside (210), has been isolated from M. boaria [74]. Compounds 4-deacetyl-10-oxo-dihydrobotrydial (211) and 4β-acetoxy-9β,10β,15α-trihydroxyp robotrydial (212) were obtained from solid cultures of an endocytic fungal strain, Phomopsis species Lz42, cultivated on M. hookeri [75] (Table 5 and Figure 5).
    Figure 5. Seven types (E1–E7) of sesqiterpenoids skeletons.
    Table 5. The sesqiterpenoids isolated from Maytenus.
    No. Name R1 R2 R3 R4 R5 R6 R7 R8 Type Ref.
    130 1α,9α-dibenzoyloxy-6β,8α,15-triacetoxy-4β-hydroxy-dihydro-β-agarofurane OBz H H OAc CH3 α-OAc α-OBz CH2OAc E1 [60]
    131 1α,9α-dibenzoyloxy-2α,6β,8α,15-tetracetoxy-4β-hydroxydihydro-β-agrofurane OBz α-OAc H OAc CH3 α-OAc α-OBz CH2OAc E1 [60]
    132 6β,8β-15-triacetoxy-1α,9α-dibenzoyloxy-4β-hydroxy-β-dihydroagarofuran OBz H H OAc CH3 β-OAc α-OBz CH2OAc E1 [61]
    133 1α,6β,8β-15-tetraacetoxy-9α-benzoyloxy-4β-hydroxy-β-dihydroagarofuran OAc H H OAc CH3 β-OAc α-OBz CH2OAc E1 [61]
    134 (1S,4S,6R,7S,8S,9R)-1,6,15- triacetoxy-8,9-dibenzoyloxy-4β-hydroxy-β-dihydroagarofuran OAc H H OAc CH3 α-OBz β-OBz CH2OAc E1 [61]
    135 (1R,2S,4S,5S,6R,7R,9S,10S)-6,15-diacetoxy-1,2,9-tribenzoyloxy-4-hrdroxy-8-oxo-dihydro-β-agarofuran OBz α-OBz H OAc CH3 O α-OBz CH2OAc E1 [41]
    136 9β-cinnamoyloxy-2β,3β-diacetoxy-6β-hydroxy-lα-nicotinoyloxydihidro-β-agarofuran ONic β-OAc β-OAc OH CH3 H β-OCin CH3 E1 [41]
    137 1α-acetoxy-2α,6β,9β-trtifuroyloxy-4β-hydroxy-dihydro-β- agarofuran OAc α-OFu H OFu CH3 H β-OFu CH3 E1 [59]
    138 1α,2α-diacetoxy-6β,9β-difuroyloxy-4β-hydroxy-dihydro-β- agarofuran OAc α-OAc H OFu CH3 H β-OFu CH3 E1 [59]
    139 1α-acetoxy-6β,9β-difuroyloxy-2α,4β-dihydroxy-dihydro-β-agarofuran OAc α-OH H OFu CH3 H β-OFu CH3 E1 [59]
    140 1α-acetoxy-2α-benzoyloxy-6β,9β-difuroyloxy-4β-dihydro-β-agarofuran OAc α-OBz H OFu CH3 H β-OFu CH3 E1 [59]
    141 1α-acetoxy-6β,9β-difuroyloxy-2α-propyonyloxy-4β-hydroxy-dihydro-β-agarofuran OAc α-OPr H OFu CH3 H β-OFu CH3 E1 [59]
    142 1α-acetoxy-6α,9β-difuroyloxy-2α-(2)-methylbutyroyloxy-4β-hydroxy-dihydro-β-agarofuran OAc α-OButMe H OFu CH3 H β-OFu CH3 E1 [59]
    143 1α, 2α,15-triacetoxy-6β,9β-difuroyloxy-4β- hydroxy-dihydro-β-agarofuran OAc α-OAc H OFu CH3 H β-OFu CH2OAc E1 [59]
    144 1α, 2α,15-triacetoxy-6β,9β-dibenzoyloxy-4β- hydroxy-dihydro-β-agarofuran OAc α-OAc H OBz CH3 H β-OBz CH2OAc E1 [59]
    145 (1R,2R,4S,5R,7S,9S,10R)-2-acetoxy-1-benzoyloxy-9-cinnamoyloxy-4-hydroxy- dihydro-β-agarofuran OBz β-OAc H H CH3 H β-OH CH3 E1 [62]
    146 (1R,2S,3S,5R,7R,9S,10R)-2-acetoxy-9-benzoyloxy-1-cinnamoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran OCin β-OAc β-ONic H CH3 H H CH3 E1 [62]
    147 (1R,2S,3S,4S,5S,6R,7R,9S,10R)-2,6-diacetoxy-1-benzoyloxy-9-cinnamoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran OBz β-OAc β-ONic OAc CH3 H β-OCin CH3 E1 [62]
    148 (1R,2S,3S,4S,5S,6R,7R,9S,10R)-2,6-diacetoxy-1,9-dibenzoyloxy-3-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran OBz β-OAc β-ONic H CH3 H β-OBz CH3 E1 [62]
    149 (1R,2S,3S,4S,5R,7S,8S,9R,10R)-2,3-diacetoxy-8,9-dibenzoyloxy-1-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran ONic β-OAc β-OAc H CH3 β-OBz β-OBz CH3 E1 [62]
    150 (1R,2S,4S,5S,6R,7R,8S,9R,10S)-6,8-diacetoxy-1,2,9-tribenzoyloxy-4-hydroxy-dihydro-β-agarofuran OBz α-OBz H OAc CH3 β-OAc β-OBz CH3 E1 [62]
    151 (1R,2S,3S,4S,5R,7S,8S,9R,10R)-2,8-diacetoxy-3,9-dibenzoyloxy-1-nicotinoyloxy-4-hydroxy-dihydro-β-agarofuran ONic β-OAc β-OBz H β-OAc β-OBz CH3 - E2 [62]
    152 (1R,2S,4R,5S,6R,7R,8S,9R,10S)-6,8-diacetoxy-1,9-dibenzoyloxy-2-nicotinoyloxy-dihydro-β-agarofuran OBz α-ONic H OAc β-OAc β-OBz CH3 - E2 [62]
    153 1α,15-diacetoxy-6β,9β-dibenzoyloxy-2α-nicotinoyloxy-dihydro-β-agarofuran OAc α-ONic H OBz H β-OBz CH3 - E2 [62]
    154 1α,15-diacetoxy-6β,9β-dibenzoyloxy-2α-nicotinoyloxy-4β-hydroxy-dihydro-β-agarofuran OAc α-ONic H OBz CH3 H β-OBz CH2OAc E1 [62]
    155 (1R,2S,4S,5S,6R,7R,9S,10S)-1,2,6,9,15-pentaacetoxy-4-hydroxy-8-oxo-dihydro-β-agarofuran OAc α-OAc H OAc CH3 O α-OAc CH2OAc E1 [63]
    156 (1R,2S,4S,5S,6R,7R,9S,10S)-1,2,9,15-taacetoxy-4,6-dihydroxy-8-oxo-dihydro-β-agarofuran OAc α-OAc H OH CH3 O α-OAc CH2OAc E1 [63]
    157 (1R,2S,4S,5S,6R,7R,9S,10S)-1,9,15-triacetoxy-2,4,6-trihydroxy-8-oxo-dihydro-β-agarofuran OAc α-OH H OH CH3 O α-OAc CH2OAc E1 [63]
    158 (1R,2S,3S,4S,5S,6R,7R,9S,10S)-1,2,3,6,9,12,15-heptaacetoxy-4-hydroxy-8-oxo-dihydro-β-agarofuran OAc α-OAc β-OAc OAc CH2OAc O α-OAc CH2OAc E1 [63]
    159 1α,2α,3β,6β,8α,9α,12,15-octaacetoxy-4β-hydroxy-dihydro-β-agarofuran OAc α-OAc β-OAc OAc CH2OAc α-OAc α-OAc CH2OAc E1 [63]
    160 (1S,4S,5S,6R,7R,8S,9R,10R)-8-acetoxy-1,9-dibenzoyloxy-6-nicotynoyloxy-dihydro-β-agarofuran OBz H H ONic α-OAc α-OBz CH3 - E2 [49]
    161 (1S,4R,5R,6R,7R,8S,9R,10R)-8-acetoxy-1,9-dibenzoyloxy-4-hydroxy-nicotynoyloxy-dihydro-β-agarofuran OBz H H ONic CH3 α-OAc α-OBz CH3 E1 [49]
    162 (1R,2S,4S,5S,6R,7R,9S,10R)-1,15-diacetoxy-2,6-dibenzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OAc α-OBz H OBz CH3 H α-OFu CH2OAc E1 [64]
    163 (1R,2S,4S,5S,6R,7R,9S,10R)-1,2,15-triacetoxy-6-benzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OAc α-OAc H OBz CH3 H α-OFu CH2OAc E1 [64]
    164 (1R,2S,4S,5S,6R,7R,9S,10R)-1,15-diacetoxy-6-benzoyloxy-9-(3-furoyloxy)-2,4-dihydroxy-dihydro-β-agarofuran OAc α-OH H OBz CH3 H α-OFu CH2OAc E1 [64]
    165 (1R,2S,4S,5S,6R,7R,9S,10R)-1,15-diacetoxy-6,9-dibenzoyloxy-2,4-hydroxy-dihydro-β-agarofuran OAc α-OH H OBz CH3 H α-OBz CH2OAc E1 [64]
    166 (1R,2S,4S,5S,6R,7R,9S,10R)-1,2,6,15-tetracetoxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OAc α-OAc H OAc CH3 H α-OFu CH2OAc E1 [64]
    167 (1R,2S,4S,5S,6R,7R,9S,10R)-1-Acetoxy-2,6-dibenzoyloxy-9-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OAc α-OBz H OBz CH3 H α-OFu CH3 E1 [64]
    168 (1S,2S,3S,4S,5R,7R,9S,10R)-2,3-diacetoxy-9-benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OFu β-OAc β-OAc H CH3 H α-OBz CH3 E1 [64]
    169 (1S,2R,4S,5R,7R,9S,10R)-2-acetoxy-9-benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OFu β-OAc H H CH3 H α-OBz CH3 E1 [64]
    170 (1S,2R,4S,5R,7R,9S,10R)-2-Acetoxy-1,9-di-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OFu β-OAc H H CH3 H α-OFu CH3 E1 [64]
    171 (1S,2R,4S,5R,7R,9S,10R)-2-Acetoxy-9-trans-cynamoiloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OFu β-OAc H H CH3 H α-OCin CH3 E1 [64]
    172 (1S,4S,5R,7R,9S,10S)-9-Benzoyloxy-1-(3-furoyloxy)-4-hydroxy-dihydro-β-agarofuran OFu H H H CH3 H α-OBz CH3 E1 [64]
    173 (1S,2R,3R,4R,5S,7R,9S,10R)-2,3-diacetoxy-9-benzoyloxy-1-(3-furoyloxy)-dihydro-β-agarofuran OFu β-OAc β-OAc H H α-OBz CH3 - E2 [64]
    174 (1S,2R,4R,5S,7R,9S,10R)-2-Acetoxy-9-benzoyloxy-1-(3-furoyloxy)-dihydro-β-agarofuran OFu β-OAc H H H α-OBz CH3 - E2 [64]
    175 1α,2α,9β,15-tetracetoxy-8β-benzoyloxy-β-dihydroagarofuran OAc α-OAc H H β-OBz α-OAc CH2OAc - E2 [65]
    176 1α-benzoyloxy-2α,6β,8α-triacetoxy-9α-methyllbutyroyloxy-β-dihydroagarofuran OBz α-OAc H OAc α-OAc α-OMeBut CH3 - E2 [65]
    177 1α,6β-diacetoxy-2α,8α,9α-tribenzoyloxy-β-dihydroagarofuran OAc α-OBz H OAc α-OBz α-OBz CH3 - E2 [65]
    178 1α-benzoyloxy-2α,6β,8α,9α-tetraacetoxy-β-dihydroagarofuran OBz α-OAc H OAc α-OAc α-OAc CH3 - E2 [65]
    179 1α,6β,8α-triacetoxy-9α-benzoyloxy-2α-hydroxy-β-dihydroagarofuran OAc α-OH H OAc α-OAc α-OBz CH3 - E2 [65]
    180 (1R,2S,4R,5S,6R,7R,8R,9S,10S)-1,6-diacetoxy-8,9-dibenzoyloxy-2-h ydroxy-β-d ihydroagarofuran OAc α-OH H OAc α-OBz α-OBz CH3 - E2 [65]
    181 1α,6β,15-triacetoxy-8α-methylbutyroyloxy-9α-benzoyloxy-2α-hydroxy-β-dihydroagaro-furan OAc α-OH H OAc α-OMeBut α-OBz CH2OAc - E2 [65]
    182 1α,6β,15-triacetoxy-8α,9α-dibenzoyloxy-2α-hydroxy-β-dihydroagarofuran OAc α-OH H OAc α-OBz α-OBz CH2OAc - E2 [65]
    183 1α,6β,8β,15-tetracetoxy-2α-hydroxy-9α-benzoyloxy-β-dihydroagarofuran OAc α-OH H OAc β-OAc α-OBz CH2OAc - E2 [65]
    184 Chiapens A OH α-OAc H OAc α-OBz α-OBz CH2OAc - E2 [66]
    185 Chiapens B OAc α-OAc H OAc α-OBz α-OBz CH2OAc - E2 [66]
    186 Chiapens C OH H H OAc α-OBz α-OBz CH2OAc - E2 [66]
    187 Chiapens D OAc α-OAc H OBut H α-OBz CH2OAc - E2 [66]
    188 Chiapens E OAc α-OAc β-OAc OAc O α-OBz CH2OAc - E2 [66]
    189 1α,6β-diacetoxy-8α-hydroxy-9β-furoyloxy-β-agarofuran OAc H H OAc α-OH β-OFu CH3 - E2 [67]
    190 1α-acetoxy-6β,8α-dihydroxy-9β-furoyloxy-β-agarofuran OAc H H OH α-OH β-OFu CH3 - E2 [67]
    191 1α-benzoyloxy-2α,3β,6β,9β,14-pentaacetoxy-8-oxo-β-agarofuan OBz α-OAc β-OAc OBz O OAc CH2OAc - E2 [67]
    192 1α-furoyloxy-2α,3β,6β,9β,14-pentaacetoxy-8-oxo-β-agarofuan OFu α-OAc β-OAc OFu O OAc CH2OAc - E2 [67]
    193 Bilocularins A OAc H H OAc α-OH α-OBz CH2OAc - E2 [68]
    194 Bilocularins B OAc H H OH α-OAc α-OBz CH2OAc - E2 [68]
    195 Bilocularins C OAc H H OAc O α-OBz CH2OAc - E2 [68]
    196 Bilocularins D OHAc α-OAc H OAc CH3 H β-OtCin CH2OBz E1 [69]
    197 Bilocularins E OHAc α-OAc H OAc CH3 H β-OtCin CH2OtCin E1 [69]
    198 Bilocularins F OHAc α-OAc H OAc CH3 H β-OtCin CH2OH E1 [69]
    199 Bilocularins G OAc α-OAc H OAc CH3 H β-OtCin CH2OAc E1 [69]
    200 Bilocularins H OAc α-OH H OAc CH3 H β-OtCin CH2OH E1 [69]
    201 Bilocularins I OAc α-OH H ONic CH3 H β-OtCin CH3 E1 [69]
    202 (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9,10-trihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]-oxepin-5-yl furan-3-carboxylate OAc H H OH CH3 α-OH β-OFu CH3 E1 [70]
    203 (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diylbis(furan-3-carboxylate) OAc H H OFu CH3 α-OH β-OFu CH3 E1 [71]
    204 (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate) OAc H H OFu CH3 H β-OFu CH3 E1 [71]
    205 (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]-oxepin-5-yl furan-3-carboxylate OAc H H OBz CH3 H β-OFu CH3 E1 [71]
    206 2β,6β-diacetoxy-1α,9β-dibenzoyl-3β-hydroxy-dihydro-β-agarofuran α-OBz β-OAc β-OH H β-CH3 - - - E3 [72]
    207 1α,2α,6β,8α-tetraacetoxy-9β-benzoyl-15-hydroxy-dihydro-β-agarofuran α-OAc α-OAc H α-OAc α-CH2OH - - - E3 [72]
    208 1α,2α,6β,8α,15-pentaacetoxy-9β-benzoyl-dihydro-β-agarofuran α-OAc α-OAc H α-OAc α-CH2OAc - - - E3 [72]
    209 1β-acetoxy-9α-benzoyloxy-2β,6α-dinicotinoyioxy-β-dihydro-agarofuran(heterophylline) - - - - - - - - E4 [73]
    210 Boarioside - - - - - - - - E5 [74]
    211 4-deacetyl-10-oxo-dihydrobotrydial - - - - - - - - E6 [75]
    212 4β-acetoxy-9β,10β,15α-trihydroxyp robotrydial - - - - - - - - E7 [75]

    2.3. Alkaloids

    2.3.1. Sesquiterpene Pyridine Alkaloids

    Among the naturally occurring nitrogen containing compounds, the pyridine alkaloids constitute an important group, and these are relatively rare natural products. The Celastraceae family is a rich source of sesquiterpene pyridine alkaloids. These compounds are endowed with a novel type of chemical diversity, and have complicated stereo-chemistries. They also possess a broad spectrum of biological activities, such as having immunosuppressive and anti-tumor properties. The vast majority of macrolide sesquiterpene pyridine alkaloids, from the genus Maytenus, are based on the [5,11-epoxy-5β,10a-eduesman-4(14)-ene] skeleton known as dihydro-β-agarofum. These compounds are characterized by a pyridine dicarboxylic acid macrocyclic bridge (such as evoninic, wilfordic and hydroxywilfordic acids), linked via two ester moieties at the C-3 and C-15 positions [65][76]. Many of these alkaloids have been isolated by organic chemists over recent years. Below we summarize their information, including the names of compounds, their original plant source as well as their structures.
    The potent anti-feedant wilforine (213) was isolated from M. rigida [77]. Compounds emarginatines A–H (214–221) and emarginatinine (222) were obtained from M. emarginata and the leaves of M. diversifolia. [11][22][78][79]. Ebenifoline W-I (223), ebenifoline E-I (224) and ebenifoline E-II (225) were separated from the stem bark methanol extracts of M. ebenifolia Reiss [80]. Compounds aquifoliunines E-I-IV (226–229) have been obtained from the root barks of M. aquiJolium. [81][82], while ilicifoliunines A–B (230–231) and mayteine (232) were isolated from the root barks of M. ilicifolia [83]. Laevisines A (233) and B (234) have been separated from the CHCl3:MeOH (9:1) extracts of the barks of M. laevis [84]. Compounds mekongensine (235), 7-epi-mekongensine (236), 1-O-benzoyl-1-deacetylmekongensine (237), 9′-deacetoxymekongensine (238), 1-O-benzoyl-1-deacetyl-9′-deacetoxymekongensine (239), 7-epi-euojaponine A (240), 2-O-benzoyl-2-deacetylmayteine (241) and 7-epi-5-O-benzoyl-5-deacetylperitassine A (242) have been isolated from the roots of M. mekongensis [85]. The compound 5-benzoyl-5-deacetylwilforidine (243) was isolated from M. buchananii (Loes.) R. Wilczek. This appears to be the first sesquiterpene nicotinoyl alkaloid found which was based on hydroxywilfordic acid, with a benzoyl group at C-5 position [86]. Compounds putterines A (244) and B (245) have been separated from the roots of M. putterlickoides [76]. The compound 7-(acetyloxy)-O11-benzoyl-O2,11-deacetyl-7-deoxoevonine (246) was isolated from the methanol extracts of the barks of the Colombian medicinal plant, M. laevis [52]. Chiapenines ES-I (247), ES-II (248), ES-III (249) and ES-IV (250) were isolated from the leaves of M. chiapensis [87]. Compound jelskiine (251) was obtained from M. jelskii and M. cuzcoina [88]. Compounds O9-benzoyl-O9-deacetylevonine (252) and 8β-acetoxy-O1-benzoyl- O1-deacetyl-8-deoxoevonine (253) have been separated from the organic extracts of the roots of M. spinosa [24]. Compounds 1α,2α,6β,8β,9α,15-hexacetoxy-4β-hydroxy-3β,13-[2′-(3-carboxybutyl)] nicotinicacid-dicarbo-lactone-β-dihydroagarofuran (254), 1α,2α,9α,15-tetracetoxy-4β,6β-dihydroxy-8-oxo,3β,13-[4′-(3-carboxybutyl)]nicotinicacid-dicarbolactone-β-dihydroagarofuran (255), 1α,2α,9α,15-tetracetoxy-4β,6β,8β-trihydroxy-3β,13-[4′-(3-carboxybutyl)] nicotinicacid-dicarbolactone-β-dihydroagarofuran (256) and 1α,2α,8β,9α,15-pent acetoxy-4β,6β-dihydroxy-3β,13-[4′-(3-carboxybutyl)] nicotinicaciddicarbolactne-β-dihydroagarofuran (257) were isolated from the leaves of M. spinosa [65]. Compounds 4-deoxyalatamine (258), 1-O-benzoyl-1-deacetyl-4-deoxy-alatamine (259), 1,2-O-dibenzoyl-1,2-deacetyl-4-deoxyalatamine (260) and 4-deoxyisowilfordine (261) were obtained from an ethyl acetate extract of M. oblongata stems [31] (Table 6 and Figure 6).
    Figure 6. Fifteen types (F1–F15) of sesquiterpene pyridine alkaloids skeletons.
    Table 6. The sesquiterpene pyridine alkaloids isolated from Maytenus.
    No. Name R1 R2 R3 R4 R5 Type Ref.
    213 Wilforine - - - - - F1 [77]
    214 Emarginatine-A OAc OAc OAc H OAc F2 [78]
    215 Emarginatine-B OAc Benzoate H OAc OAc F2 [78]
    216 Emarginatine-C OAc OH OAc H OAc F2 [79]
    217 Emarginatine-D OA OAc OAc H OAc F2 [79]
    218 Emarginatine-E OH OH H OAc OAc F2 [79]
    219 Emarginatine-F Molecules 26 04563 i003 OAc H OH OAc F2 [11]
    220 Emarginatine-G CH3CH=CCH3OO OAc OAc H OAc F2 [11]
    221 Emarginatine-H OAc OAc OAc H OH F2 [22]
    222 Emarginatinine - - - - - F3 [79]
    223 Ebenifoline W-I β-OAc OBz OBz OAc - F4 [80]
    224 Ebenifoline E-I β-OAc OAc OH OBz OAc F5 [80]
    225 Ebenifoline E-II β-OAc OBz OAc OBz OAc F5 [80]
    226 Aquifoliunine E-I α-OBz OAc OAc OAc CH2OAc F5 [81]
    227 Aquifoliunine E-II α-OH OAc OH OAc CH2OAc F5 [81]
    228 Aquifoliunine E-III α-OH OAc OAc OAc CH2OAc F5 [82]
    229 Aquifoliunine E-IV α-ONic OAc OAc OAc CH2OAc F5 [82]
    230 Ilicifoliunines A α-OBz OH OAc OAc CH2OAc F5 [83]
    231 Ilicifoliunines B α-OBz OAc OAc CH2OAc - F4 [83]
    232 Mayteine β-OAc OAc OAc OBz CH2OAc F5 [83]
    233 Laevisines A β-OAc OAc OAc OCOC(CH3)=CHCH3 CH2OAc F5 [84]
    234 Laevisines B β-OAc OAc ONic CH2OAc - F4 [84]
    235 Mekongensine Ac H OAc OAc - F6 [85]
    236 7-epi-mekongensine Ac OAc H OAc - F6 [85]
    237 1-O-benzoyl-1-deacetylmekongensine Bz H OAc OAc - F6 [85]
    238 9′-deacetoxymekongensine Ac H OAc H - F6 [85]
    239 1-O-benzoyl-1-deacetyl-9′-deacetoxymekongensine Bz H OAc H - F6 [85]
    240 7-epi-euojaponine Bz Ac H OAc H F7 [85]
    241 2-O-benzoyl-2-deacetylmayteine Bz Bz Ac H OAc F7 [85]
    242 7-epi-5-O-benzoyl-5-deacetylperitassine A - - - - - F8 [85]
    243 5-benzoyl-5-deacetylwilforidine - - - - - F9 [86]
    244 Putterines A Molecules 26 04563 i004 OAc COOCH3 COOCH3 CH2OAc F5 [76]
    245 Putterines B Molecules 26 04563 i005 OAc COOCH(CH3)2 COOCH3 CH2OAc F5 [76]
    246 7-(acetyloxy)-O11-benzoyl-O2,11-deacetyl-7-deoxoevonine β-OAc OAc OH OAc CH2OBz F5 [52]
    247 Chiapenines ES-I OBz OBz α-OAc - - F10 [87]
    248 Chiapenines ES-II OBz OBz =O - - F10 [87]
    249 Chiapenines ES-III OBz OH =O - - F10 [87]
    250 Chiapenines ES-IV OAc OH =O - - F10 [87]
    251 Jelskiine OiBut α-OAc OH OAc - F11 [88]
    252 O9-benzoyl-O9-deacetylevonine OBz =O OAc OAc - F11 [24]
    253 8β-acetoxy-O1-benzoyl- O1-deacetyl-8-deoxoevonine OAc β-OAc OAc OBz - F11 [24]
    254 1α,2α,6β,8β,9α,15-hexacetoxy-4β-hydroxy-3β,13-[2′-(3-carboxybutyl)]nicotinicacid-dicarbo-lactone-β-dihydroagarofuran - - - - - F12 [65]
    255 1α,2α,9α,15-tetracetoxy-4β,6β-dihydroxy-8-oxo,3β,13-[4′-(3-carboxybutyl)]nicotinicacid-dicarbolactone-β-dihydroagarofuran =O - - - - F13 [65]
    256 1α,2α,9α,15-tetracetoxy-4β,6β,8β-trihydroxy-3β,13-[4′-(3-carboxybutyl)]nicotinicacid-dicarbolactone-β-dihydroagarofuran β-OH - - - - F13 [65]
    257 1α,2α,8β,9α,15-pent acetoxy-4β,6β-dihydroxy-3β,13-[4′-(3-carboxybutyl)]nicotinicaciddicarbolactne-β-dihydroagarofuran β-OAc - - - - F13 [65]
    258 4-deoxyalatamine OAc OAc - - - F14 [31]
    259 1-O-benzoyl-1-deacetyl-4-deoxy-alatamine OBz OAc - - - F14 [31]
    260 1,2-O-dibenzoyl-1,2-deacetyl-4-deoxyalatamine OBz OBz - - - F14 [31]
    261 4-deoxyisowilfordine - - - - - F15 [31]

    2.3.2. Maytansinoids

    In 1972, Kupchan et al. [7] found a macrolide alkaloid, maytansine (262), which was a natural product that had anti-tumor activities, and this was first isolated from M. serrata. Compound 262 is an anti-tumor agent with a novel structure, and, therefore, is of great clinical interest. Subsequently, maytansine (262), maytanprine (263) and maytanbutine (264) were isolated from M. buchananii [89]. Larson et al. [90] also isolated two new maytansinoid compounds, 2′-N-demethylmaytanbutine (265) and maytanbicyclinol (266) from M. buchananii (Figure 7).
    Figure 7. The chemical structures of maytansinoids, isolated from Maytenus.

    The entry is from 10.3390/molecules26154563

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