Eleven new alkaloids (1–11), classified as the 12-acetylplicamine (1), N-deformyl-seco-plicamine (2), plicamine (3–6), 4a-epi-plicamine (7), seco-plicamine (8), and lycorine (9–11) framework types, along with 15 known alkaloids (12–26) were isolated from the whole plants of Zephyranthes carinata. The structures of the new alkaloids 1–11 were established by extensive spectroscopic data interpretation. The absolute configurations of 9 and 10 were defined by single-crystal X-ray diffraction analysis. Zephycarinatines A (1), B (2), and G (7) represent the first examples of 12-acetylplicamine, N-deformyl-seco-plicamine, and 4a-epi-plicamine alkaloids, respectively. Alkaloids 6, 11, 17, and 20–23 exhibited AChE inhibitory activities with IC50 values ranging from 1.21 to 184.05 μM, and a preliminary structure–activity relationship is discussed.

Three novel diterpenoids with an unprecedented 2,3:5,6-di-seco-grayanane carbon skeleton, rhodomollacetals A–C (1–3), are isolated from the leaves of Rhododendron molle. Their structures are elucidated by comprehensive spectroscopic techniques and single-crystal X-ray diffraction. Rhodomollacetal A (1) possesses a novel cis/cis/cis/cis-fused 6/6/6/6/5 pentacyclic ring system, featuring an unprecedented 11,13,18-trioxa-pentacyclo [8.7.1.15,8.02,8.012,17]nonadecane scaffold. Compounds 2 and 3 have a rare 4-oxatricyclo[7.2.1.01,6]dodecane moiety and a 2,3-dihydro-4H-pyran-4-one unit. Compounds 1–3 showed moderate PTP1B inhibitory activities, and their molecular dockings were investigated.

Two diterpenoids with an unprecedented diterpene carbon skeleton, cinnamomols A (1) and B (2), were isolated from the leaves of Cinnamomum cassia. 1 and 2 feature a cage-like, rigid, 5/5/5/5/5/6-fused hexacyclic ring system. The structures of 1 and 2 were established by extensive spectroscopic techniques and single-crystal X-ray diffraction, and their plausible biosynthetic pathways were proposed. 1 and 2 exhibited significant in vitro immunostimulative activity, and the mode of action of 1 was investigated.

A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1), and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the leaves of Rhododendron molle. Their structures were elucidated using comprehensive spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5 hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated with three cyclopentane units. The plausible biosynthetic pathway for 1 was proposed. Compound 1 exhibited moderate PTP1B inhibitory activity.

•Three new Amaryllidaceae alkaloids 1–3 were isolated from Zephyranthes candida.•Compound 1 is the first example of 7-phenyl-hexahydroindole alkaloids.•Compound 3 is the first example of 5,2'-dimethyl-biphenyl-2-ylamine alkaloids.•New Amaryllidaceae alkaloid 3 has a potent AChE inhibitory activity.•Docking studies revealed that interactions with W286 and Y337 are necessary.Three new Amaryllidaceae alkaloids, named zephycandidines I−III (1–3), were isolated from Zephyranthes candida. The structures of 1−3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1H−1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. The absolute configuration of 1 was finally established by single crystal X-ray diffraction using Cu Kα radiation. Zephycandidines I (1) and III (3) with new framework types represent the first example of 7-phenyl-hexahydroindole and 5,2'-dimethyl-biphenyl-2-ylamine alkaloids, respectively, and their plausible biosynthetic pathway are proposed. Zephycandidine II (2) is the first C3a-phenyl-hexahydroindole type alkaloid isolated from the genus of Zephyranthes. These new alkaloids 1–3 were evaluated for their acetylcholinesterase (AChE) inhibitory activities, and 3 showed potent AChE inhibitory activity with an IC50 value of 8.82 μM, suggesting that the framework of 5,2'-dimethyl-biphenyl-2-ylamine in 3 may be a potential group for the AChE inhibitory activity. The docking studies of 1−3 and galanthamine with AChE revealed that interactions with W286 and Y337 are necessary for the AChE inhibitory activity.Download high-res image (302KB)Download full-size image

•Eleven grayanane and a leucothane diterpenoid were isolated from R. micranthum.•Eleven known diterpenoids were isolated from R. micranthum.•The absolute configurations of two of the grayanane diterpenoids were determined by single-crystal X-ray diffraction.•The structures of three of the grayanane diterpenoids were confirmed by single-crystal X-ray diffraction.Eleven grayanane diterpenoids, 1-epi-grayanotoxin IV, 1-epi-grayanotoxin II, 6-deoxy-1-epi-grayanotoxin XVII, 6-deoxygrayanotoxin XVII, 16-acetylgrayanotoxin II, 3-oxograyanotoxin IX, 14-deoxygrayanotoxin VIII, 14-acetylisograyanotoxin II, rhodomicranols C–E, and a leucothane diterpenoid, rhodomicranol F, together with eleven known diterpenoids were isolated from leaves of Rhododendron micranthum. Their structures were elucidated by spectroscopic analyses, with the absolute configurations of 1-epi-grayanotoxin IV and rhodomicranol C determined by single-crystal X-ray diffraction with Cu Kα radiation, and the structures of 14-acetylisograyanotoxin II and known grayanotoxins IX and X confirmed by single-crystal X-ray diffraction. All twenty-three diterpenoids were evaluated for their in vitro immunomodulatory activities, and none showed significant immunomodulatory activities in a dose-dependent manner. In addition, they are non-toxic to the murine lymphocytes in the general cytotoxicity assay.Twelve previously unknown and eleven known diterpenoids were isolated from the leaves of Rhododendron micranthum. Four of their structures were confirmed by single-crystal X-ray diffraction. Their in vitro immunomodulatory activities were evaluated.

Three new diterpenoids with unprecedented carbon skeletons, cinncassiols F (1) and G (2) and 16-O-β-d-glucopyranosyl-19-deoxycinncassiol G (3), a new isoryanodane diterpenoid, 18-hydroxyperseanol (4), six known isoryanodane diterpenoids, 5–10, and a known ryanodane diterpenoid, 11, were isolated from the stem bark of Cinnamomum cassia. Compound 1 possesses an 11,13:12,13-diepoxy-6,11-epoxy:12,13-disecoisoryanodane diterpenoid skeleton bearing ketal and hemiketal functionalities, whereas compounds 2 and 3 feature an 11,12-secoisoryanodane diterpenoid skeleton with an 11,6-lactone moiety. The structures of the four new diterpenoids, 1–4, and their absolute configurations were established using HRESIMS, NMR, ECD, single-crystal X-ray diffraction, and chemical methods. Compounds 2 and 11 significantly inhibited the proliferation of murine T cells induced by ConA.

A new diterpene with an unprecedented carbon skeleton, micranthanone A (1), two new grayanane diterpenoids bearing an unusual 5,6-(3,4-dihydroxylbenzylidene acetal) motif, rhodomicranols A (2) and B (3), and three known grayanane diterpenoids (4–6) were isolated from Rhododendron micranthum. Their structures were elucidated by spectroscopic analyses, calculated ECD, and single-crystal X-ray diffraction. The in vitro immunomodulatory activities of 1–6 were evaluated, and a plausible biogenetic pathway for 1 is proposed.

Twelve new megastigmane sesquiterpenoids, wilsonols A–L (1–12), were isolated from the leaves of Cinnamomum wilsonii, along with seven known analogues (13–19). The structures of compounds 1–12 were established by spectroscopic analyses. The absolute configurations of 1–5 were determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation, and the absolute configurations of 6–12 were determined by the modified Mosher’s method. Compounds 1–9 and 13–19 were evaluated for in vitro cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480, and compared against the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compound 13 exhibited IC50 values ranging from 2.5 to 12 μM and selectivity indices of >10 against SMMC-7721, A-549, and MCF-7 cell lines. Selected compounds were evaluated for in vitro immunomodulatory activity.

Fifteen new ent-kaurane diterpenoids, compounds 1–15, and two known analogues, 4-epi-henryine A (16) and leukamenin E (17), were isolated from the whole plants of Salvia cavaleriei. The structures of the new compounds were established by spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism and single-crystal X-ray diffraction analyses with Cu Kα radiation. Compounds 1–15 were evaluated for their cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480, as well as the noncancerous Beas-2B cell line. Compounds 1–10, 12, 14, and 15 showed broad-spectrum cytotoxicity, with compounds 1, 3, 6–10, 12, and 15 exhibiting more potent cytotoxicity than the positive control, cis-platin, with IC50 values ranging from 0.65 to 6.4 μM.

•A new guaiane sesquiterpenoid and thirteen known compounds were isolated from Teucrium viscidum.•The absolute configuration of 2 was determined by single-crystal X-ray diffraction analysis.•Compounds 12 and 13 were isolated as natural products for the first time.•All compounds were isolated from T. viscidum for the first time.A new guaiane sesquiterpenoid (1), two known guaiane sesquiterpenoids (2 and 3), and eleven known compounds (4–14), were isolated from Teucrium viscidum. Their structures were identified by spectroscopic analyses and by comparison of their spectral data with those reported in the literature. The absolute configuration of lipidiol (2) was determined by single-crystal X-ray diffraction analysis with Cu Kα radiation. Compounds 12 and 13 were isolated as natural products for the first time. All compounds were isolated from T. viscidum for the first time.A new guaiane sesquiterpenoid (1), two known guaiane sesquiterpenoids (2 and 3), and eleven known compounds (4–14), were isolated from Teucrium viscidum. Their structures were determined by spectroscopic analysis and by comparison of their spectral data with those reported in the literature. The absolute configuration of lipidiol (2) was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Compounds 12 and 13 were isolated as natural products for the first time. All compounds were isolated from T. viscidum for the first time.

•Nine germacrane sesquiterpenoids possessing an unusual Δ3-15,6-lactone moiety were isolated.•Their absolute configurations were determined by X-ray crystallography, CD, and by chemical transformation.•Chemical transformation resulted in six germacrane 6,15-diol derivatives.•Their in vitro cytotoxicity against five human cancer cell lines was evaluated.•Their in vitro immunomodulatory effects on T and B cells were evaluated.Nine germacrane sesquiterpenoids with an unusual Δ3-15,6-lactone moiety, scapiformolactones A–I (1–9), and one known seco-germacrane sesquiterpenoid, 3,7,11-trimethyldodeca-l,6,9-triene-3,11-diol (10), were isolated from whole plants of Salvia scapiformis Hance. Their structures were elucidated by spectroscopic methods including HR-ESIMS, IR, UV, NMR, and CD, as well as by quantum mechanical calculations and chemical transformations. Structures of compounds 1–3 were also confirmed by single-crystal X-ray diffraction analysis. Six germacrane 6,15-diol derivatives (11–16) were obtained by chemical transformation. Compounds 1–9 and 11–16 were evaluated for their in vitro immunomodulatory effects on T and B cells, as well as their in vitro cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480.Nine germacrane sesquiterpenoids (1–9) with an unusual Δ3-15,6-lactone moiety and one known seco-germacrane sesquiterpenoid were isolated from the whole plants of Salvia scapiformis. Six germacrane 6,15-diol derivatives (11–16) were obtained by chemical transformation. Their structures were elucidated, and their in vitro cytotoxicity against five human cancer cell lines, as well as in vitro immunomodulatory effects on T and B cells were evaluated.

Seven new alkaloids, N-methylhemeanthidine chloride (1), N-methyl-5,6-dihydroplicane (5), O-methylnerinine (6), N-ethoxycarbonylethylcrinasiadine (7), N-ethoxycarbonylpropylcrinasiadine (8), N-phenethylcrinasiadine (9), and N-isopentylcrinasiadine (10), together with eight known alkaloids, hemeanthamin (2), 3-epimacronine (3), (+)-tazettine (4), N-methylcrinasiadine (11), trisphaeridine (12), 5,6-dihydrobicolorine (13), lycorine (14), and nigragillin (15), were isolated from the whole plants of Zephyranthes candida. The structures of the new compounds were established by spectroscopic data interpretation, with single-crystal X-ray diffraction analysis performed on 1. The absolute configuration of 3-epimacronine (3) was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Compounds 1–15 were evaluated for their in vitro cytotoxicity against five human cancer cell lines and the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compounds 1, 2, 9, and 14 exhibited cytotoxicity with IC50 values ranging from 0.81 to 13 μM with selectivity indices as high as 10 when compared to the Beas-2B cell line.

Three new flavans, (2R,3R)-7-methoxy-flavan-3-ol (1), (2S)-7,3′-dihydroxy-4′-methoxyflavan 3′-O-β-d-glucopyranoside (2), (2S)-7,3′-dihydroxy-4′-methoxyflavan 7-O-β-d-glucopyranoside (3), and one known flavan (4) were isolated from the whole plants of Zephyranthes candida (Amaryllidacea). The structures of the new flavans 1–3 were determined by extensive spectroscopic analyses including HRESIMS, NMR, and electronic circular dichroism (ECD), and the absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Flavans 1–3 displayed significant inhibitory effects on the LPS-induced NO production in RAW264.7 mouse macrophages with IC50 values of 17.34, 16.14, and 21.52 μM, respectively, suggesting their potentials for anti-inflammatory agents.

Two pairs of racemic spirodienone neolignans with a rare 2-oxaspiro[4.5]deca-6,9-dien-8-one motif, named (±)-subaveniumins A (1) and B (2), were isolated from the bark of Cinnamomum subavenium. The chiral separation of the (+)-1, (−)-1, (+)-2, and (−)-2 enantiomers was accomplished via high-performance liquid chromatography on a chiral column. Their structures were elucidated using single-crystal X-ray diffraction and spectroscopic analyses (UV, IR, HRESIMS, and 1D and 2D NMR). The absolute configurations of the enantiomers were determined by comparing the experimental and calculated electronic circular dichroic spectra. The (+)-1, (−)-1, (+)-2, and (−)-2 enantiomers exhibited moderate inhibitory effects against NO production in RAW264.7 mouse macrophages induced by lipopolysaccharide, with IC50 values of 17.9, 5.6, 15.1, and 4.3 μM, respectively.