Stereoselective production of (S)-1-aralkyl- and 1-arylethanols by freshly harvested and lyophilized yeast cells

Substituted (S)-1-phenyl- 2a–h and (S)-1-benzyl-propan-2-ols 4a and b, and (S)-1-phenylethanol 6 were produced from prochiral ketones 1a–h, 3a,b and 5 by reductions with freshly harvested Zygosaccharomyces rouxii and Debaryomyces hansenii cells. The bioreductions were also performed by lyophilized cells. Comparison of the secondary alcohols from the bioreductions 2b–e,g,h and 4a and authentic (S)-alcohols (S)-2b–e,g,h and (S)-4a synthesized from enantiopure (S)-methyloxirane 7 proved the absolute configuration of the products.     

Briaviodiols B–E,new anti-inflammatory hydroperoxyfurancembranoids from Briareum violaceum

Four new hydroperoxyfurancembranoids, briaviodiols B–E (1–4), were obtained from an octocoral identified as Briareum violaceum. The structures of cembranoids 1–4 were established by using spectroscopic methods and comparing the spectroscopic data with those of known related analogues. Compounds 1, 3, and 4 were found to exhibit significant in vitro anti-inflammatory activity in LPS-induced RAW 264.7 macrophage cells by inhibiting the expression of iNOS protein.     

Enantioselective hydrolyses with Yarrowia lipolytica: a versatile strain for esters,enol esters,epoxides, and lactones

Racemic secondary esters 1–3, γ-lactones 8–9, and styrene oxide 7 are kinetically resolved via hydrolysis with Yarrowia lipolytica YL2 strain. The enantioselective hydrolysis of prochiral enol esters 4–6 to the corresponding homochiral carbonyl compounds 13–15 is also described. Subsequent reduction of the ketone 13 and of the aldehyde 15 can be avoided using lyophilised cells.     

The synthesis and bioevaluation of the dicyclic arene-homospermidine conjugates

Four novel dicyelic arene-homospermidine conjugates (6a-d) were synthesized and evaluated for cytotoxicity in L1210,α- difluoromethylomithine (DFMO) treated L1210,melanoma B16,spermidine (SPD) treated B16,and Hela cells.In the DFMO- treated L1210 experiments,6a-d were more sensitive to DFMO than naphthalene-homospermidine (6e),suggesting that 6a-d can utilize the polyamine transporter (PAT) to enter the cells as well as 6e.The diminished cytotoxicity in the SPD/B16 experiments also supported this conclusion.In summary,the homospermidine is an efficacious vector to ferry dicyclic arches into cells via PAT.     

Isolation and structures of biselyngbyasides B,C, and D from the marine cyanobacterium Lyngbya sp., and the biological activities of biselyngbyasides

Bioassay-guided fractionation of the marine cyanobacterium Lyngbya sp. led to the isolation of biselyngbyasides B (3), C (4), and D (5), novel analogs of biselyngbyaside (1) and biselyngbyolide A (2). The gross structures of 3–5 were determined by NMR spectral analyses, and their stereochemistries were established based on NOESY spectra and CD data. Biselyngbyasides (1–3) showed growth-inhibitory activity and apoptosis-inducing activity against both HeLa S₃ cells and HL60 cells. The fura-2 method revealed that biselyngbyasides (1–3) increased the cytosolic Ca²⁺ concentration in HeLa S₃ cells.     

A pair of new enantiomeric hybrid phthalide–adenines with a rare 5-oxa-1-azaspiro[3,4]octane moiety and two pairs of new enantiomeric hybrid paraethyl phenol–adenines from Ligusticum chuanxiong

Three pairs of new enantiomeric adenine alkaloids, (+)/(?)-liguadenines A–C [(+)/(?)-1–3], were isolated from the rhizome of Ligusticum chuanxiong Hort. The structures and absolute configurations of these compounds were determined using spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism analyses. To the best of our knowledge, compounds (+)-1 and (?)-1 are the first hybrid phthalide–adenines to be ever reported. The linkage between the phthalide and adenine units in these compounds forms a rare 5-oxa-1-azaspiro[3,4]octane moiety. Analyses of the anti-inflammatory activities of the isolated compounds show that (+)/(?)-1 and (+)-3 exhibit significant inhibitory activity against LPS-induced TNF-α and IL-6 production in RAW264.7 cells. RT-qPCR analysis confirms that the most active compound, (+)-3, exerts anti-inflammatory activity by downregulating the mRNA expressions of TNF-α and IL-6 in the cells.     

Five undescribed plant-derived bisphenols from Artemisia capillaris aerial parts: Structure elucidation,anti-hepatoma activities and plausible biogenetic pathway

Yin-Chen, which belongs to the Asteraceae family and the genus Artemisia, is among the most abundantly used traditional medicines in China for the treatment of hepatitis and bilious disorder. Herein, five undescribed plant-derived bisphenols, capillarisenols A–E (13, 15, 25, 29, 31), and one undescribed phenolic compound (32), together with 32 known phenolic compounds (1–12, 14, 16–24, 26–28, 30, 33–38), were isolated and identified based on spectroscopic evidence from aerial parts of Artemisia capillaris Thunb. Capillarisenols A–E are the type of bisphenols firstly isolated from this plant. The plausible biogenetic pathway of new compounds was also proposed. In addition, the potential anti-hepatoma effects on Huh7 and HepG2 cell lines of all isolated compounds were evaluated in vitro. Capillarisenol C (25) showed significant anti-hepatoma activity in Huh7 and HepG 2 cells, with IC₅₀ values of 4.96 and 8.58 μM, better than the positive control drug (Lenvatinib). This study provided phytochemical evidence for further development and utilisation of A. capillaris in health products.     

Alkaloids of NIRAM,natural dye from Polygonum tinctorium,and their anti-inflammatory activities

Phytochemical investigation of EtOH extract of NIRAM, natural dye from Polygonum tinctorium, resulted in the purification of nine alkaloid compounds (1–9) including four new compounds (1–4). Structures of these new compounds were elucidated by 1D and 2D NMR (¹H and ¹³C NMR, ¹H–¹H COSY, ¹H–¹³C HSQC, ¹H–¹³C HMBC), IR, UV, HR-ESI-MS, and ECD spectra. Isolated compounds (1–9) were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells. Compounds 1–3, 5, and 7 showed potent NO production inhibitory activities, with IC₅₀ values of 3.88–22.87 μM.     

Boesenberols I–K,new isopimarane diterpenes from Boesenbergia pandurata with TRAIL-resistance overcoming activity

TRAIL is a promising anticancer agent due to its unique ability to kill tumor cells selectively without harming non-malignant cells. However, some cancer cells are reported to be TRAIL-resistant. Searching potent TRAIL agonist to overcome resistance is an important strategy for its successful use as an anticancer agent. As a part of our continuous research on natural inhibitors, activity-guided fractionation of the MeOH extract of Boesenbergia pandurata rhizomes afforded three (1–3) new isopimarane diterpenes, boesenberols I–K, together with two (4–5) known compounds. The structures of these new compounds were elucidated using HRESIMS, IR, 1D and 2D NMR spectroscopy. All compounds showed TRAIL-resistance overcoming activity.     

Phenolic compounds of Solanum xanthocarpum play an important role in anti-inflammatory effects

Solanum xanthocarpum is used for the treatment of rheumatic arthritis, toothache, sore throats, carbuncle, furuncle, and other inflammatory diseases in traditional Chinese medicine and Ayurvedic medical system, with the phenolic compounds being one of its principal components. In this study, 51 phenolic compounds including seven new compounds 1, 2, 9, 13, 17, 22, and 40 were isolated from the fruits of Solanum xanthocarpum. 40 known compounds 3–8, 10–12, 14–16, 18–21, 23–25, 28–32, 35–39, 41–51 were firstly isolated from Solanum xanthocarpum. Their structures were determined by comprehensive spectroscopic analyses, X-ray crystallography, NMR calculations, chemical methods, and comparisons of spectroscopic data. The results of anti-inflammatory assays indicated that most isolated compounds (3–7, 11–30, 32–37, 39, 40, 42, 43, 45, and 48–51) possessed significant inhibitory activities of the NO release of LPS-induced RAW 264.7 cells, with IC₅₀ values ranging from 10.46 to 47.59 μM. Further analysis by molecular docking implied that most bioactive compounds could interact with the amino acid residues of iNOS proteins, supporting the anti-inflammatory activity of the compounds. Especially, compounds 17–20, 26–27, 32, and 34 showed strong affinities with iNOS proteins. The bioinformatic analysis further revealed the potential anti-inflammatory targets of the phenolic compounds isolated from the fruits of Solanum xanthocarpum.     

Nectrianolins A,B, and C,new metabolites produced by endophytic fungus Nectria pseudotrichia 120-1NP

Two sesquiterpene-epoxycyclohexenone conjugates, nectrianolins A (1) and B (2), together with a sesquiterpene, nectrianolin C (3), were isolated from the brown rice culture of Nectria pseudotrichia 120-1NP, an endophytic fungus isolated from Gliricidia sepium. Their structures were determined on the basis of 1D-/2D-NMR spectroscopy and HRESIMS data analyses in combination with chemical means. Nectrianolins A–C (1–3) exhibited cytotoxic activity against both HL60 and HeLa cells.     

Trichiliasinenoids A–C,three 6,7-secomexicanolide limonoids with a 7,29-linkage from Trichilia sinensis

Trichiliasinenoids A–C (1–3), three new limonoids with an unprecedented C-29-C-7 connecting carbon skeleton formed by migration of C-7 from C-6 to C-29 of a mexicanolide-type limonoid precursor were isolated from the leaves and twigs of Trichilia sinensis. Their structures were assigned by spectroscopic analysis, and the absolute configurations were determined by X-ray crystallography (1) and ECD calculation (2 and 3). A possible biosynthetic pathway of 1 was also proposed. Compound 2 exhibited moderate cytotoxicity against HL-60 cells and weak cytotoxicity against SMMC-7721cells.     

New bioactive pyrrospirones C−I from a marine-derived fungus Penicillium sp. ZZ380

Seven rare pyrrospirones C?I (1–7) as well as 18 known compounds were isolated from a marine-derived fungus Penicillium sp. ZZ380. Structures of the new pyrrospirones were elucidated by extensive NMR spectroscopic analyses, HRESIMS data, and Mosher's method. Pyrrospirone D (2) was also confirmed by X-ray diffraction analysis. Pyrrospirone G (5) showed potent activity in inhibiting the proliferation of different glioma cells with IC₅₀ values of 1.06–8.52 μM and pyrrospirones C (1), F (4), and I (7) had antimicrobial activity against the growth of both methicillin-resistant Staphylococcus aureus and Escherichia coli with MIC values of 2.0–5.0 μg/mL.     

Distachydrimanes A–F,phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum

By integrating one strain-many compounds (OSMAC) and LC–MS-based molecular networking strategies, distachydrimanes A–F (1–6), six novel phenylspirodrimane dimers and hybrids representing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the modified fermented rice substrate of a coral-derived fungus Stachybotrys chartarum. All the structures incorporating their absolute configurations were elucidated based on comprehensive spectroscopic analyses, mainly including HRESIMS and NMR data, single-crystal X-ray diffraction (Cu Kα), and comparison of the experimental electronic circular dichroism (ECD) data. Architecturally, compounds 1–6 represent an unprecedented class of dimeric phenylspirodrimanes with an unexpected C-18–C-23′ linkage, of which compounds 1–3 also feature an unexpected 5-methyl-1,3-benzenediol moiety via a carbon-carbon linkage. The bioactivity assay demonstrated that compounds 1, 5 and 6 induced cell proliferation inhibition, G0/G1 cell cycle arrest, senescence and mitochondrial-mediated apoptosis in L1210 cells, highlighting their potentials as a new category of anticancer agents.     

Resolution of 1-arylalkylamines with 3-O-hydrogen phthalate glucofuranose derivatives: role of steric bulk in a family of resolving agents

The development of three new acidic resolving agents which are hydrogen phthalates of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose 1, 1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranose 2 and 1,2-O-cyclohexylidene-5,6-O-diphenylmethylidene-α-d-glucofuranose 3 is shown for the resolution of 1-arylalkylamines 7a–k. The salts between 1, 2 and (RS)-1-arylalkylamines 7a–k selectively crystallize 1·(S) 7a–j and 2·(S) 7a–h salts, allowing us to recover the corresponding bases (S) 7a–j and (S) 7a–h, respectively, in good yield and enantiomeric excess (73–95% ee). Whereas, the salts between 3 and (RS)-1-arylalkylamines 7a–c,g–i,k selectively crystallize 3·(S)-7a–c,g–i salts to recover the corresponding bases (S)-7a–c,g–i in poor enantiomeric excess (4–35% ee). The difference between the resolving ability of 1 and 2 for 1-arylalkylamines 7a–h is very slight, but there is considerable difference compared to ortho-substituted 1-arylalkylamines 7i and 7j. The role of substituents on a family of resolving agents 1, 2 and 3 is also discussed to interpret their resolving ability.     

Euphorane C,an unusual C17-norabietane diterpenoid from Euphorbia dracunculoides induces cell cycle arrest and apoptosis in human leukemia K562 cells

Four new polycyclic diterpenoids euphoranes A ? D (1–4), together with 12 known terpenoids (5–16) were isolated from the whole plants of Euphorbia dracunculoides. Compound 2 represents the first example of aromatic 15,16,17-trinorabietane diterpenoid in Euphorbia species, and euphorane C (3) is an unusual 17-norabietane diterpenoid. The absolute configurations of 1, 2, and 4 were determined by single crystal X-ray diffraction, while that of 3 was established with the aid of ECD and 1D NMR quantum chemical calculation. Moreover, the absolute stereochemistry of 11 was demonstrated for the first time by crystallographic data. Compounds 1–16 were screened for antiproliferative activities against five human cancer cell lines, and 3 showed significant cytotoxicity against the human leukemia K562 cells with IC₅₀ value of 3.59 μM. Preliminary mechanistic investigation revealed that 3 could induce cell cycle arrest at G0/G1 phase and apoptosis in K562 cells.     

Novel quinolinone alkaloids bearing a lignoid moiety and related constituents in the leaves of Melicope denhamii

Six novel quinolinone alkaloids bearing a phenylpropanoid or a coumarin moiety, named melicodenines C–H (1–6), two new cinnamyl alcohol derivatives, named melicodins A (7) and B (8), and a new coumarinolignan, named melicodin C (9), were isolated from the leaves of Melicope denhamii (Seem.) T. G. Hartley. Their structures were established by spectroscopic analyses including extensive 2D-NMR experiments. Compounds 1–5 and 9 possess a cyclobutane ring and are hypothetically produced by a [2+2] cycloaddition, whereas compound 6 is presumed to form through a Diels–Alder cycloaddition followed by the elimination of an acetone molecule. Ten quinolinone alkaloids (1–6, 10–13) and a coumarinolignan (9) were tested for anti-proliferative activity against DLD-1 human colon cancer cells. Melicodenine G (5) showed the most potent inhibitory activity, causing the induction of apoptosis with an IC₅₀ value of 9.4±0.3 μM.     

Neuroprotective constituents from the fruits of Maclura tricuspidata

Cudraisoflavone L ? T (1–11), cudradihydrochalcone A (12), and cudrabibenzyl A (13), together with 41 known constituents, were isolated from the fruits of Maclura tricuspidata (formerly known as Cudrania tricuspidata). Their structures were determined by spectroscopic and chemical methods including electronic circular dichroism. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells, of these six compounds exhibited activities with EC₅₀ values of 4.5–18.6 μM. Furthermore, the neuroprotective effects against oxygen glucose deprivation (OGD)-induced cell death of all isolated constituents, together with 37 previously reported isoflavones were evaluated. Four compounds showed neuroprotective activities with EC₅₀ values of 3.5–11.9 μM.     

Structural elucidation,antioxidant and hepatoprotective activities of chemical composition from Jinsi Huangju (Chrysanthemum morifolium) flowers

Six new compounds (huangjusus A-F), including three caffeic acid glycosides (1–3), one quinic acid derivative (4), one dihydroflavone glycoside (11) and one monoterpene (31), together with thirty-eight known compounds (5–10, 12–30, 32–44), were obtained from “Jinsi Huangju” (Chrysanthemum morifolium Ramat.) flowers. Their structures were elucidated on the basis of the data obtained from different spectroscopic techniques. Among these compounds, five new (1–4 and 11) and ten known (5–9, 12, 13, 17, 40, and 42) compounds demonstrated significant 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging effects with IC₅₀ values of 4.22–19.90 μM. Furthermore, three new compounds (1, 11, and 31) and seven known compounds (13, 19, 21, 29, 30, 39, and 41) exhibited potent hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with the cell survival rates of 61.53 %, 63.55 %, 60.01 %, 63.05 %, 59.75 %, 59.15 %, 61.07 %, 62.72 %, 58.86 %, and 58.76 % (positive control bicyclol, 58.41 %), respectively, at a concentration of 10 μM. These results indicate the potency of the flowers against radicals and in hepatoprotections.     

Conformational study of α-arylethylamides of (−)-camphanic acid

The absolute conformation and configuration of diastereomeric amides (4A,B–6A,B) of (1S,3R)-camphanic acid (lactone of 1-hydroxy-2,2,3-trimethylcyclopentan-1,3-dicarboxylic acid, (−)-camphanic acid 9) with α-arylethylamines 1–3 are deduced from ¹H NMR data and MM2 calculations. The α-arylethyl group in diastereomers A and B adopt nearly opposite absolute conformations, stabilized by hydrogen bonding in the syn-oriented O–C(1)–C(6)–N–H unit, and repulsive interaction between the 1′C–Me group and the amide CO group. The absolute configuration (1′S) is assigned to the 4A–6A diastereomers, and the (1′R)-configuration to the 4B–6B diastereomers; this assignment is confirmed by the preparation of 4A and 5A from enantiomerically pure (1′S)-α-arylethylamines 1 and 2, respectively. These results also enabled the assignment of pro-R (H_R) and pro-S (H_S) protons in the benzyl derivative 7.