Chuktabularins A-D, four new limonoids with unprecedented carbon skeletons from the stem bark of Chukrasia tabularis

Chuktabularins A-D (1-4), four novel 16-norphragmalin-type limonoids that feature unprecedented skeletons with a biosynthetically extended C2 or C3 unit at C-15 forming a unique 2,7-dioxabicyclo[2.2.1]heptane moiety, were isolated from the stem bark of Chukrasia tabularis. Their structures were elucidated by spectroscopic analysis and computer modeling. The biosynthetic pathway of 1-4 was postulated.     

Chukvelutilides A-F, phragmalin limonoids from the stem barks of Chukrasia tabularis var. velutina

Chukvelutilides A-F (1-6), a new class of C-15-acyl phragmalin type limonoids, featuring a C-16/C-30 δ-lactone ring, were isolated from Chukrasia tabularis var. velutina. These compounds are suggested to possess a three- or four-carbon enolized acyl substituent at C-15 through a plausible biosynthetic origin. Their structures were elucidated by extensive spectroscopic means, and that of 1 was confirmed by single-crystal X-ray diffraction.     

Velutabularins A-J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina

Velutabularins A-J, ten novel phragmalin-type limonoids, were isolated from the stem bark of Chukrasia tabularis var. velutina. In structures of 1-6, the tetrahydrofuran ring from dehydration of OH-15 and OH-17, ring C and 13/14/18-cyclopropanyl moiety formed an unprecedented 8-oxatricyclo[4,3,1^1,6]decane. Compounds 7-10 are derivates of 1-6 opening the tetrahydrofuran ring. All of these compounds possess a novel C-16/C-30 δ-lactone ring, which were reported in phragmalins rarely. The structures of these novel compounds were elucidated based on extensive 1D and 2D spectroscopic analysis. The absolute configuration of 5 and 9 were determined by the calculated electronic circular dichroism (ECD) method. The anti-inflammatory activities of major compounds (2, 4, 5, 9) were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line.     

Ivorenoids A–F: limonoids from Khaya ivorensis

Six new limonoids, ivorenoids A–F (1–6), along with ten known analogues, were isolated from an ethanolic extract of the stems of Khaya ivorensis. Their structures were elucidated on the basis of spectroscopic analyses. Compounds 1 and 2 possessed a rare rearranged skeleton of khayanolides and a unique γ-lactone (C-16/C-8) replacing the common and characteristic δ-lactone D-ring (C-16/C-17) of limonoids. A mechanism of the interesting deuteration of H-2 and H-15β of 1, and H-15β of the solvent CD₃OD due to the keto–enol tautomerism was demonstrated. Compounds 3 and 6 showed moderate activity against HL-60 cell line with IC₅₀ values of 15.3 and 17.5 μM, respectively.     

Aphanamolide A, a new limonoid from Aphanamixis polystachya

Two new limonoids, namely aphanamolides A (1) and B (2), were isolated from the seeds of Aphanamixis polystachya . Their structures were established by spectroscopic methods. Aphanamolide A (1) featured an unprecedented carbon skeleton via the formation of a C-3-C-6 bond. Compounds 1 and 2 showed cytotoxic activity against two tumor cell lines.     

Swiemahogins A and B, two novel limonoids from Swietenia mahogani

Two novel limonoids, swiemahogins A (1) and B (2) isolated from the twigs and leaves of Swietenia mahogany, are the first examples of andirobin and phragmalin types of limonoids, of which the D-ring δ-lactone is demolished and a rare γ-lactone is fused to the C-ring at C-8 and C-14. Their structures were elucidated by extensive spectroscopic means, and that of 1 was confirmed by single-crystal X-ray diffraction.     

Exploration of possible biosynthetic origin of 1/8/9-orthoester moiety in phragmalins

The orthoester, a functional group that features three alkoxy groups attaching to a single carbon atom, was an important structural subunit discovered in plant resource. Diverse phragmalin-type limonoids with different orthoester moiety and connected locations have been isolated from the Meliaceae family. Under the guidance of plausible biosynthetic pathway, phragmalin-type 1/8/9-orthoesters were effectively synthesized from its phragmalin mother nuclear through a key intermediate with an esterfunction at C-1. These interesting findings indicated that natural phragmalin-type 1/8/9-orthoesters were derived from phragmalins with esterified substituent at C-1 and hydroxyl groups at C-8 and C-9.     

Chuktabrins A and B, two novel limonoids from the twigs and leaves of Chukrasia tabularis

Two novel limonoids, chuktabrin A (1), featuring the unique motifs of a 1,3-dioxolan-2-one and a 3,4-dihydro-2 H-pyran, and chuktabrin B (2), possessing an unprecedented polycyclic skeleton, were isolated from Chukrasia tabularis. The structures of 1 and 2 bearing a biosynthetically extended C3 and C2 unit at C-15, respectively, were elucidated on the basis of spectroscopic data, and that of 1 was confirmed by a single-crystal X-ray diffraction.     

Protolimonoids and norlimonoids from the stem bark of Toona ciliata var. pubescens

Six new tirucallane protolimonoids, toonapubesins A-F (1-6), one new rearranged tirucallane protolimonoid, toonapubesin G (7), and two new 21,22,23-trinorapotirucallane limonoids, toonapubesic acids A (8) and B (9), possessing an unprecedented carbon skeleton, along with five known tirucallane protolimonoids (10-14) and one known apotirucallane limonoid (15), were isolated from the stem bark of Toona ciliata var. pubescens. Their structures and relative configurations were determined by detailed spectroscopic analysis and by chemical methods. The proposed structures of 8 and 11 were confirmed by X-ray diffraction analysis of their respective derivatives (8a and 11a). The absolute configuration of 8 was determined by a novel solid-state TDDFT ECD approach on its derivative 8a while the absolute configuration of 10 was determined by the modified Mosher's method. In addition, the structures of dyvariabilin H (10c) proposed by Sticher et al. and cneorin-NP(36) (11b) by Mondon et al. were corrected as 10 and 11, respectively. Toonapubesin G (7) showed promising inhibitory activity against CDC25B with an IC(50) value of 2.1 μM, while compound 8a showed significant cell protecting activity against H(2)O(2)-induced SH-SY5Y cell damage with 11.5% increase in cell viability.     

Aphanalides A–H,ring A-seco limonoids from the fruits of Aphanamixis polystachya

Eight new ring A-seco limonoids, aphanalides A–H (1–8) were isolated from the fruits of Aphanamixis polystachya. Aphanalides A–C (1–3) are the first examples of ring A-seco limonoids with an unusual oxetane ring between C-7 and C-14. The structures of aphanalide A (1) and aphanalide C (3) were confirmed by single-crystal X-ray studies. Their structures including absolute stereochemistry were established on the basis of extensive NMR spectroscopic analysis, by comparison of experimental and calculated electron circular dichroism (ECD) and by X-ray diffraction, representing the first report of assignment of absolute configuration of such type ring A-seco limonoids. The biogenetic origin of aphanalides A–D (1–4) from aphanalides E–H (5–8) was also postulated.     

Chukrasones A and B: Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis

Two new limonoids, chukrasone A (1) incorporating a highly rearranged A/B ring system and chukrasone B (2) possessing the first 16,19-dinor limonoid backbone with an extended C3 unit at C-15, were isolated from Chukrasia tabularis. Their structures were characterized on the basis of detailed spectroscopic analysis. Compounds 1 and 2 exhibited potential inhibition of the delayed rectifier (I(K)) K(+) current.     

Labdane diterpenes from the rhizomes of Hedychium coronarium

A new labdane diterpenoid, (E)-labda-8(17),12-dien-15,16-olide (1) together with eight known compounds, coronarin D (2), coronarin D methyl ether (3), coronarin D ethyl ether (4), isocoronarin D (5), coronarin B (6), labda-8(17),11,13-trien-15,16-olide (7), (E)-labda-8(17),12-diene-15,16-dial (8) and 16-hydroxylabda-8(17),11,13-trien-15,16-olide (9), are isolated from the rhizomes of Hedychium coronarium. Compounds 2-4, 5 and 9 are isolated as mixtures of C-15, C-14 and C-16 epimers, respectively. Their structures are determined on the basis of their spectroscopic data. The epimeric mixtures of 2 and 3 have not been reported before. Some of them were evaluated for their cytotoxicity.     

Ceramicine A and walsogyne A, novel limonoids from two species of Meliaceae

Two novel limonoids, ceramicine A (1) without any methyls at C-4, and walsogyne A (2) with a ring C-seco limonoid, have been isolated from the barks of Chisocheton ceramicus and Walsura chrysogyne, respectively, and the structures were fully elucidated on the basis of spectroscopic data. Ceramicine A (1) and walsogyne A (2) showed a moderate cytotoxic activity.     

Antifouling activity of simple synthetic diterpenoids against larvae of the barnacle Balanus albicostatus Pilsbry

Five new pimarane diterpenoids 1-5 were synthesized using ent-8(14)-pimarene-15R,16-diol as starting material. The structures were elucidated by means of extensive NMR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. Compounds 1-3 and 5 showed more potent antifouling activity than capsaicin. Compound 5, which exhibited almost the same antifouling activity as starting material, showed better stability than starting material. These compounds all showed antifouling activity in a non-toxic way against larval settlement of the barnacle B. albicostatus. Analysis of structure-activity relationships (SAR) demonstrated that the substituents on the C-15 and C-16 position of pimarane diterpenoid were responsible for the antifouling activity.     

Cytotoxic limonoids from Brazilian Melia azedarach

Three new C-seco limonoids (1-3) and one new tetracyclic limonoid (4) were isolated from a methanol extract of the ripe fruits of Melia azedarach collected in Curitiba, Brazil, and their structures were elucidated by spectroscopic data analysis and comparison of spectral data with those of the previously known compounds. Among the limonoids isolated in the present study, compounds 3 and 4 exhibited significant inhibitory activity against HeLa S3 cancer cells, whereas 1 and 2 showed weak cytotoxicity.     

Diverse Ring-seco Limonoids from Munronia unifoliolata and Their Biological Activities

Twenty-two new limonoids,mufolinoids A—V(1—22),including six rings A,B-seco limonoids(1—6),twelve ring A-seco limonoids(7—18),four ring-intact limonoids(19—22),together with thirteen known compounds(23—35)were isolated from Munronia unifoliolata.Their structures including absolute configurations were elucidated by combination of NMR,HR-MS,single-crystal X-ray diffraction and calculations of ECD and NMR technologies.Compounds 24,25,33,34 could be significantly reversed the multidrug resistance of MCF-7/doxorubicin(DOX)cells,and the reversal fold(RF)was much higher than that of positive drug Verapamil.Compounds 24,28,and 29 exhibited significant anti-inflammatory activity with the IC50 values in the range of 17.7—39.4μmol/L.Furthermore,compound 29 could markedly inhibit the release of IL-1βby inhibiting the initiation and assembly of NLRP3 inflammasome,which demonstrates the great potential of limonoids as an anti-inflammatory agent.     

Kv1.2 potassium channel inhibitors from Chukrasia tabularis

Eighteen new limonoids, chubularisins A-R (1-18), along with eleven known analogues, were isolated from the stem bark of Chukrasia tabularis. The structures of 1-18 were elucidated on the basis of spectroscopic data and chemical evidence. Compound 1 represented the first example of 8,9,12-orthoester of phragmalin limonoids. Interestingly, compounds 4, 8, and 22 exhibited potent and selective inhibition against the delayed rectifier (I(K)) K(+) current with IC(50) values of 0.61, 2.03, and 2.15 μM, respectively.     

Two new limonoids from Munronia henryi

Two new limonoids, munronolide (1) and munronolide 21-O-beta-D-glucopyranoside (2), were isolated from the whole plant of Munronia henryi (Meliaceae). Their structures have been elucidated on the basis of spectroscopic and chemical methods. The D-glucose moiety attached to C-21 position of limonoid is firstly reported.     

Fragmentation Study of Limonoids from Turraae pubescens by Electrospray Ionization Quadrupole Time-of-flight Mass Spectrometry

Nine representative limonoids isolated from Turraae pubescens were investigated by electrospray ionization quadrupole time-of-flight tandem mass spectrometry in positive ion mode. Although the structures of these compounds are similar, the corresponding fragmentation patterns and mass spectrometry and tandem mass spectrometry (MS/MS) spectra are clearly different. For Turrapubin A–C, product ions can be detected in both low and high mass ranges. A McLafferty-type rearrangement is the only way for the cleavage of C9–C10. For 11-epi-toonacilin, Turrapubin E, Turraflorin A, 11-epi-23-hydroxytoonacilide, Turrapubin H and 11-epi-21-hydroxytoonacilide, the cleavage of C9–C10 goes through two different ways, including McLafferty-type rearrangement and homolytic cleavage. The relative abundances of product ions from McLafferty-type rearrangement for 11-epi-toonacilin, 11-epi-23-hydroxytoonacilide, and Turrapubin H are high, while those for Turrapubin E, Turraflorin A, and 11-epi-21-hydroxytoonacilide are low. A pair of epimers was distinguished unambiguously by MS/MS spectra. It was found that the substituent group at C-1, hydroxy group, O atom linked to C-14 and C-15, and the oxygenated furan ring were the important factors leading to the differences of their MS/MS spectra.     

The bakkenolides from the root of Petasites formosanus and their cytotoxicity.

Thirty-two new bakkenolides, bakkenolides-Db (1)--Dh(7), -Fa(8), -Fb(9), -I(10)--M(14), -Na(15), -Nb(16), -O(17)--T(22), -Ua (23), -Ub(24), -V(25)--X(27), -Ya(28), -Yb(29), -Za(30), -Zb(31) and -III(32), from the roots of Petasites formosanus together with thirty known compounds were isolated. The structures were characterized by spectral analysis. The locations, C-1 and/or C-9 of bakkenolide skeleton, of the substituents, such as acetoxy, isobutyroyloxy and isovaleroyloxy groups, can be determined by the chemical shifts of their signals and the H-1 and/H-9 in the 1H-NMR spectra. The cytotoxicity was also discussed.