Brønsted Acid-Mediated Conversion of Naturally Abundant Lathyrane Diterpenes: Are Rare 10,11-seco-Lathyrane Diterpenes Artifacts?

The question of whether rare 10,11-seco-lathyranes are natural products or artifacts is thoughtfully considered after a Brønsted acid-mediated chemical conversion of naturally abundant 5/11/3 lathyrane type diterpenes into 10,11-seco-lathyranes was developed. Benefiting from this concise route, a series of 10,11-seco-lathyrane products (1-14) were smoothly synthesized. The conversion may involve an acid promoted cyclopropane ring opening accompanied by a double bond shift with final trapping of carbocation. The ease of this chemical conversion under mildly acidic conditions may imply that the 10,11-seco-lathyranes isolated to date are artifacts. This work not only develops a new modular synthetic strategy for efficient constructing rare 10,11-seco-lathyranes, but also provides a promising bioactive diterpene with excellent effect against the NO production on LPS-induced BV-2 cells.

Photo-induced scandium-catalyzed biomimetic skeleton conversion of lathyrane to naturally rare eupholathone Euphorbia diterpenes.

The naturally scarce eupholathone-type euphornin E (1) was efficiently prepared from abundant lathyrane-type Euphorbia factor L1via a visible-light-induced Sc(OTf)3-catalyzed tandem process. Eupholathones 2 and 3 were also smoothly obtained by changing the reaction solvent. This route provides a convenient method for easily constructing scarce eupholathone- from lathyrane-type Euphorbia diterpenes, and confirms the biogenetic relationship between them from a chemical standpoint. Notably, compound 1 exhibited good anti-HIV activity.

Adenophorone, An Unprecedented Sesquiterpene from Eupatorium adenophorum: Structural Elucidation, Bioinspired Total Synthesis and Neuroprotective Activity Evaluation.

(-)-Adenophorone (1), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.05,9 ]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio- and stereoselective hydrogenation, and subsequent merged MBH-Tsuji-Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)-euptox A (2) in 8 steps from commercially available monoterpene (-)-carvone (6), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2, a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1. Additionally, compound 1 showed potent neuroprotective activity in H2 O2 -treated SH-SY5Y and PC12 cells.

Supramolecular structure, in vivo biological activities and molecular-docking-based potential cardiotoxic exploration of aconine hydrochloride monohydrate as a novel salt form.

Despite the high profile of aconine in WuTou injection, there has been no preparative technology or structural studies of its salt as the pharmaceutical product. The lack of any halide salt forms is surprising as aconine contains a tertiary nitrogen atom. In this work, aconine was prepared from the degradation of aconitine in Aconiti kusnezoffii radix (CaoWu). A green chemistry technique was applied to enrich the lipophilic-poor aconine. Reaction of aconine with hydrochloride acid resulted in protonation of the nitrogen atom and gave a novel salt form (C25H42NO9+·Cl-·H2O; aconine hydrochloride monohydrate, AHM), whose cation in the crystal structure was elucidated based on extensive spectroscopic and X-ray crystallographic analyses. The AHM crystal had a Z' = 3 structure with three independent cation-anion pairs, with profound conformational differences among the aconine cations. The central framework of each aconine cation was compared with that of previously reported aconitine, proving that protonation of the nitrogen atom induced the structure rearrangement. In the crystal of AHM, aconine cations, chloride anions and water molecules interacted through inter-species O-H...Cl and O-H...O hydrogen bonds; this complex hydrogen-bonding network stabilizes the supramolecular structure. The seriously disordered solvent molecules were treated using the PLATON SQUEEZE procedure [Spek (2015). Acta Cryst. C71, 9-18] and their atoms were therefore omitted from the refinement. Bioactivity studies indicated that AHM promoted in vitro proliferative activities of RAW264.7 cells. Molecular docking suggested AHM could target cardiotoxic protein through the hydrogen-bonding interactions. The structural confirmation of AHM offers a rational approach for improving the pharmaceutical technology of WuTou injection.

Aphicidal Activity of an Ageraphorone Extract From Eupatorium adenophorum Against Pseudoregma bambucicola (Homoptera: Aphididae, Takahashi).

The bamboo aphid, Pseudoregma bambucicola, is an important insect pest of bamboo that affects normal bamboo growth and induces sooty molds. The control of P. bambucicola involves the application of chemicals, such as imidacloprid, to which many species are resistant. In this study, we isolate a novel botanical pesticide (9-oxo-10,11-dehydro-ageraphorone) from an Eupatorium adenophorum(Asteraceae: Compositae) petroleum ether extract and test the aphicidal activity of this compound against P. bambucicola in laboratory bioassay and field-based experiments. This ageraphorone compound at a concentration of 2 mg/ml caused 73.33% mortality (corrected mortality [Subtracted the mortality of the negative control]: 70%) of P. bambucicola by laboratory bioassay within 6 h. Even at lower concentrations, this compound caused greater 33% mortality (corrected mortality: 30%) of aphids. Field experiments with naturally infested bamboo plants showed that two applications of 2 mg/ml ageraphorone to infested plants completely cleared infestations within 30 d. These effects were similar to those of the positive control (imidacloprid). These results reveal that 9-oxo-10,11-dehydro-ageraphorone exhibits significant aphicidal activity against bamboo aphids. We suggest that future research be directed at developing this ageraphorone compound from E. adenophorum as an aphicidal agent for biocontrol.

Majusine D: A New C19-diterpenoid Alkaloid from Delphinium majus.

A new C19-diterpenoid alkaloid, designated as majusine D (1), has been isolated from Delphinium majus W. T. Wang. The structure was elucidated by detailed NMR-spectroscopic studies.

Isolation and identification of acaricidal compounds in Eupatorium adenophorum petroleum ether extract and determination of their acaricidal activity against Psoroptes cuniculi.

We used multiple silica gel column chromatography and thin-layer chromatography coupled with (1)H nuclear magnetic resonance (NMR) and (13)C NMR to separate and identify the active acaricidal ingredients in Eupatorium adenophorum petroleum ether extract. The acaricidal activity of each compound was tested against Psoroptes cuniculi in vitro. Three compounds had strong acaricidal activity against P. cuniculi in vitro. The insecticidal effect of 0.5% compound 9ß-hydroxy-ageraphorone was better than the insecticidal effect of fenvalerate, and compounds 9-oxo-ageraphorone and 9-oxo-10,11-dehydro-ageraphorone exhibited higher insecticidal effects than 9ß-hydroxy-ageraphorone. Thus, the E. adenophorum petroleum ether extract contains an effective composition of acaricides that could potentially be developed as a promising plant-origin acaricide.

Acaricidal activity of petroleum ether extracts from Eupatorium adenophorum against the ectoparasitic cattle mite, Chorioptes texanus.

In this study, we evaluated the acaricidal efficacy of extracts obtained from the plant Eupatorium adenophorum against the common cattle mite Chorioptes texanus. The results showed that 95% ethanol extracts at concentrations of 1.0, 0.5, and 0.25 g/mL (w/v) were highly toxic to C. texanus in vitro, killing 100% of mites in 4 h. Similarly, petroleum ether extracts of E. adenophorum resulted in between 80 and 100% mortality of mites in vitro at concentrations of 0.1, 0.05, and 0.025 mL/mL (v/v) within 4 h. In clinical trials, all infected individuals completely recovered after two treatments administered at 7-day intervals and remained disease-free at 60 days posttreatment. The clinical effect of treatment with E. adenophorum petroleum ether extracts was similar to that of treatment with the acaricide fenvalerate. These results indicated that E. adenophorum contains novel potential acaricidal compounds that can effectively control mites in livestock.

Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma.

Conventional liver targeted system focuses on delivering drugs to liver, bringing toxicity on hepatic normal tissues. The purpose of this study is to construct a new system capable of specially targeting to hepatic carcinoma instead of the whole liver. Based on the fact that nanoparticles (NPs) bound with either biotin or avidin tend to accumulate in tumors and avidin-attached reagents were quickly eliminated from blood circulation and assembled in liver, trans-resveratrol loaded chitosan nanoparticles (CS-NPs), CS-NPs with the surface modified either by biotin (B-CS-NPs) or by both biotin and avidin (A-B-CS-NPs) were prepared and their physiochemical properties were investigated. The in vitro release profiles of the three NPs all conformed to bioexponential equation. Pharmacokinetic experiment indicated that A-B-CS-NPs rapidly assembled in liver after injection, with the highest liver targeting index of 2.70, while the modification of biotin attenuated the liver targeting ability of NPs. Inhibitory study on HepG2 cells declared that compared to trans-resveratrol solution and CS-NPs, both B-CS-NPs and A-B-CS-NPs significantly improved the anticancer activity. When incubated with HepG2 cells at high concentration for longer time, A-B-CS-NPs exhibited superior cytotoxicity than B-CS-NPs. This study exclaims that A-B-CS-NPs may be a potent drug delivery vector specially targeting to hepatic carcinoma.

Carmichaeline A: a new C20-diterpenoid alkaloid from Aconitum carmichaeli.

The roots of Aconitum carmichaeli Debx. are known for their medicinal value. A new C20-diterpenoid alkaloid designated as carmichaeline A (1) has been isolated, along with eight known diterpenoid alkaloids from the roots of the plant. Their structures were elucidated on the basis of spectroscopic data interpretation.

Trehalose dihydrate from Tremella fuciformis.

The title compound, C(12)H(22)O(11)·2H(2)O {systematic name: 6,6'-oxybis[2-(hy-droxy-meth-yl)-3,4,5,6-tetra-hydro-2H-pyran-3,4,5-triol] dihydrate}, is a disaccharide, which was isolated from Tremella fuciformis. The mol-ecule contains two six-membered rings, both of which adopt a chair conformation. Extensive O-H⋯O hydrogen bonds occur in the crystal structure.

Neoline from Aconitum flavum Hand.

The title compound, C(24)H(39)NO(6) [systematic name: (1α,6α,14α,16ß)-N-ethyl-6,16-dimeth-oxy-4-meth-oxy-methylaconitane-1,8,14-triol], is a C(19)-diterpenoid alkaloid from the roots of Aconitum flavum Hand. The mol-ecule has an aconitane carbon skeleton with four six-membered rings and two five-membered rings. Both five-membered rings adopt envelope conformations. Two six-membered rings adopt chair conformations, whereas the other two adopt boat conformations. Intra-molecular O-H⋯O and O-H⋯N and inter-molecular O-H⋯O hydrogen bonds are present in the structure. In the crystal, one methyl group is disordered over two sites with an occupancy ratio of 0.70 (3):0.30 (3).

C19-Diterpenoid alkaloids from Delphinium umbrosum.

Three new C(19)-diterpenoid alkaloids, umbrosumines A-C (1-3), and 11 known compounds (4-14) were isolated from the roots of Delphinium umbrosum. Their structures were elucidated on the basis of the spectroscopic data interpretation.

Bonvalotidine A acetone solvate from Delphinium bonvalotii Franch.

THE TITLE COMPOUND (SYSTEMATIC NAME: 5,6ß-dihy-droxy-1α,14α,16ß-trimeth-oxy-4-methyl-7ß,8-methyl-enedi-oxy-20-ethyl-aconitan-6-yl acetate acetone monosolvate), C(27)H(41)NO(8)·C(3)H(6)O, was isolated from Delphinium bonvalotii Franch, and is a typical C(19)-diterpenoid alkaloid. The mol-ecule has a lycoctonine carbon skeleton with four six-membered rings and three five-membered rings. Three six-membered rings adopt the chair conformations while the fourth adopts a boat conformation, while the five-membered rings have the envelope conformations. The solvent mol-ecule links with the organic mol-ecule via a classical O-H⋯O hydrogen bond. Weak C-H⋯O hydrogen bonding is present in the structure. An intra-molecular O-H⋯O hydrogen bond also occurs.

Diterpenoid Alkaloids from Delphinium majus.

From the whole herbs of Delphinium majus, three new C(19)-diterpenoid alkaloids, majusines A-C (1-3), and six new C(20)-diterpenoid alkaloids, majusimines A-D (4-7) and majusidine A and B (8 and 9), have been isolated, together with 15 known compounds. The structures of compounds 1-9 were elucidated by spectroscopic data interpretation.

(1ß,2α,3α,7α,11α,13ß)-1,3,7,11-Tetra-acet-oxy-2,13-bis-(benz-yloxy)-21-methyl-19,21-secohetisan-19-al hemi-hydrate.

In the crystal structure of the title compound, C(43)H(46)NO(13)·0.5H(2)O, the mol-ecule assumes a U-shaped conformation, the terminal benzene rings being approximately parallel and partially overlapped with each other. The mol-ecule contains eight alicyclic and heterocyclic rings. The cyclo-hexane rings adopt chair conformations, the other three six-membered carbocyclic rings form a bicyclo-[2.2.2]octane system with a boat conformation for each six-membered ring, the six-membered heterocyclic ring has a chair conformation and both of the five-membered rings have envelope conformations. The solvent water mol-ecule links with the organic mol-ecule via classic O-H⋯O and weak C-H⋯O hydrogen bonding in the crystal structure.