Biosynthesis of plaunotol in Croton stellatopilosus proceeds via the deoxyxylulose phosphate pathway

Plaunotol, an acyclic diterpene alcohol that accumulates in the chloroplasts of Croton stellatopilosus leaves, was studied for its origin of isoprene units. Separate feedings of [U-¹³C]glucose and [1-¹³C]glucose into cut shoots of the plant showed that the labels from glucose were incorporated into plaunotol. NMR analysis of the purified plaunotol revealed that all four isoprene units of the molecule had the same labeling pattern which is consistent with exclusive acquisition via the deoxyxylulose phosphate pathway. The results of in vivo feeding experiments suggested that there was no significant metabolite exchange taking place between the mevalonate pathway and the deoxyxylulose pathway during the biosynthesis of plaunotol in this Croton stellatopilosus.     

Crotomacrine, a new clerodane diterpene from the fruits of Croton macrostachyus

A new clerodane diterpene, crotomacrine 1, together with the known crotepoxide were isolated from the fruits of Croton macrostachyus. Their structures were elucidated on the basis of spectral evidence.     

A crotofolane-type diterpenoid and a rearranged nor-crotofolane-type diterpenoid with a new skeleton from the stems of Croton cascarilloides

From the stems of Croton cascarilloides collected in the Okinawa Islands, a structurally rare crotofolane-type diterpenoid (1) and a rearranged nor-crotofalane, a new skeletal diterpenoid (2) were isolated. The structures were determined by X-ray crystallographic analyses, establishing their absolute stereostructures for the first time. Compound 2 was probably biosynthesized from 1 through several steps, such as decarboxylation, oxidation, C-C bond migration.     

Labdanecaryophyllic acid, a novel cytotoxic C35 terpenoid from Calocedrus macrolepis var. formosana

Chemical investigation of the bark of Calocedrus macrolepis var. formosana, an endemic tree in Taiwan, has led to the isolation of a novel terpenoid 1. Compound 1 with a rare C₃₅ skeleton constructed by a diterpene and a sesquiterpene moieties. Its structure was elucidated by spectroscopic interpretations. The anti-proliferation activity of 1 against human oral epidermoid carcinoma KB cells was evaluated, and the IC₅₀ value was determined to be 9.2 ± 0.4 μM.     

3,4-seco-Diterpenoids from Trigonostemon flavidus

Phytochemical investigation on the stems of Trigonostemon flavidus resulted in the isolation of five new 3,4-seco-diterpenoids, trigoflavidones A-E (1-5), structurally related to the main co-occurring known 3,4-seco-sonderianic acid (6) and 3,4-seco-sonderianol (7). Compound 4 possesses new 3,4-seco rearranged ent-pimarane skeletal type, characteristic of a vinyl group at C-8, while 5 features a unique five-membered ring (C₁) fused with a cyclopropane ring (C₂). The structures of the new compounds were established by a combination of spectroscopic data and computational methods. Compounds 1-7 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines.     

Biosynthesis of the triterpenoids, botryococcenes and tetramethylsqualene in the B race of Botryococcus braunii via the non-mevalonate pathway

The green microalga Botryococcus braunii race B accumulates two types of triterpenoid hydrocarbons, botryococcenes and tetramethylsqualene. Both triterpenoids are synthesized via the non-mevalonate pathway.     

Isolation and structure determination of new 4,12-dideoxyphorbol esters from Euphorbia pannonica Host.

Phytochemical study of the aerial parts of Euphorbia pannonica led to the isolation of two new tigliane diterpenes, 4,12-dideoxy(4β)phorbol-20-benzoate-13-isobutyrate (1) and 4,12-dideoxy(4β)phorbol-20-benzoate-13-isovalerianate (2). The structures and relative stereochemistry were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments (¹H NMR, JMOD, COSY, NOESY, HSQC and HMBC).     

Lannotinidines A-G, new alkaloids from two species of Lycopodium

Seven new Lycopodium alkaloids, lannotinidines A-G (1-7), have been isolated from the club moss Lycopodium annotinum and L. annotinum var. acrifolium. Stereochemistry of 1-7 was elucidated by combination of NOESY correlations and chemical transformation. Lannotinidines B-E (2-5) elevated NGF mRNA expression.     

Cyclohexadepsipeptides from Acremonium sp. BCC 28424

Six new cyclohexadepsipeptides, beauvenniatins A-E (1-5), and beauvericin J (6), together with the known beauvericin (7) and enniatin B (8), were isolated from the fungus Acremonium sp. BCC 28424. The productions of minor derivatives 3-6, possessing an N-methyl-l-tyrosine, were enhanced by feeding l-tyrosine in the liquid fermentation medium. Antimalarial, antitubercular, and cytotoxic activities of these cyclodepsipeptides were evaluated.     

Highly efficient immobilization of Cinchona alkaloid derivatives to silica gel via click chemistry

Click chemistry was adapted to the immobilization of various Cinchona alkaloid derivatives bearing alkyne functionality onto azide-modified silica gel surfaces. The developed protocol employs very mild reaction conditions, with catalytic amounts of copper(I) iodide (1-5 mol %) in acetonitrile at room temperature, ensuring complete chemical integrity of the multi-functional ligands. The utility of this approach is demonstrated by the attachment of didehydroquinine tert-butylcarbamate to azido-grafted silica gel to produce an effective chiral stationary phase for HPLC enantiomer separation. A comparison of the chromatographic behavior of this click-immobilized phase with that of a commercially available thioether-linked chiral stationary phase revealed very similar performance characteristics for various model analytes. This observation suggests that the click-immobilization may offer an appealing alternative to the established silica gel-grafting technologies, allowing for the specific benefits of high and readily controllable loading levels under noninvasive conditions.     

Three new Lycopodium alkaloids from Huperzia carinata and Huperzia squarrosa

Eleven Lycopodium alkaloids with lycodine-type, lycopodine-type, and fawcettimine-related skeletons were isolated from the whole plants of Huperzia carinata (Desv. Ex. Poir.) Trevis and Huperzia squarrosa (G. Forst) Trevis (Huperziaceae). Among them, 8,15-dihydrohuperzine A (2), lycocarinatine A (3), and lycoposerramine U N-oxide (11) are new compounds. The structures of these new alkaloids were elucidated on the basis of 2D NMR correlations. Some of these isolated alkaloids were assayed for acetylcholinesterase (AChE) inhibitory activity.     

Pressurized fluid extraction of carotenoids from Haematococcus pluvialis and Dunaliella salina and kavalactones from Piper methysticum

Pressurized fluid extraction (PFE) was examined as an alternative technology for the extraction of carotenoids in the green algae Haematococcus pluvialis and Dunaliella salina and kavalactones in Piper methysticum. The extraction process was optimized by varying the key extraction factors of solvent, sample-solvent ratio, temperature, and time. The selectivity and efficiency of extraction parameters were determined with high performance liquid chromatography (LC) and LC-mass spectrometry (LC-MS). Results showed that PFE utilization of conventional solvents under controlled temperature and pressure in an oxygen and light-free environment could result in the use of less solvent in a shorter period of time. PFE showed higher or equal extraction efficiencies as compared with traditional solvent extractions while maintaining the integrity of chemical components. PFE showed high potential for extraction of natural products and nutraceuticals, particularly labile and light sensitive chemicals.     

New tri- and tetracyclic diterpenes from Euphorbia villosa

Three new tetracyclic diterpenes were isolated from the chloroform-soluble extract of Euphorbia villosa, together with one new and one known lathyrane diterpene. The structures were elucidated by means of various spectroscopic methods, including HREI-MS, HRFAB-MS, UV, and 1D and 2D NMR techniques. Spectral analyses revealed that two of the tetracyclic compounds contain the rare 5-6-6-4 fused ring system, while the third has a 5-6-7-3 fused diterpene core. Such diterpene skeletons have previously been found only in euphoractines A-E isolated from Euphorbia micractina. As a new structural feature, the diterpene framework described here has a C-2 epimer configuration. The new lathyrane diterpene is a diester of a hitherto unknown polyfunctional parent alcohol.     

Three novel 3,4-seco-podocarpane trinorditerpenoids from Aleurites moluccana

Three novel 3,4-seco-podocarpane-type trinorditerpenoids, moluccanic acid (1), moluccanic acid methyl ester (2), and 6,7-dehydromoluccanic acid (3), were isolated from the twigs and leaves of Aleurites moluccana. Their structures were elucidated by spectroscopic methods including 2D NMR analysis. The cytotoxicity of compounds 1-3 was evaluated.     

A new approach to construction of isoindolo[1,2-a]isoquinoline alkaloids Nuevamine, Jamtine, and Hirsutine via IMDAF reaction

The interaction between 1-furyl-1,2,3,4-tetrahydroisoquinolines and unsaturated acids derivatives (acryloyl, methacryloyl, and crotonoyl chloride, maleic and citraconic anhydride) was studied. It was shown that the reaction proceeds via amide formation and subsequent intramolecular Diels-Alder reaction of the furan (IMDAF). The [4+2] cycloaddition proceeded under mild reaction conditions (25-80 °C) and afforded only the exo-adduct in a high yield. With this method, a new approach to the isoindolo[1,2-a]isoquinoline system, the basic structural element of alkaloids Jamtine, Hirsutine, and Nuevamine, is proposed.     

Hupermine A,a novel C16N2-type Lycopodium alkaloid from Huperzia phlegmaria

A novel C₁₆N₂-type Lycopodium alkaloid consisting of a quinolizidine with a 6-dimethylaminohexyl side chain, hupermine A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae

Analysis of the terpene metabolites of Pseudopterogorgia elisabethae collected from the Florida Keys has resulted in the identification of a novel hydroxyquinone, elisabethadione (1), as well as new pseudopterosins and seco-pseudopterosins. Anti-inflammatory assays indicate that elisabethadione is more potent than the well characterized pseudopterosin A and E. This report also describes the co-occurrence of pseudopterosins and seco-pseudopterosins, diterpenes with amphilectane and serrulatane skeletons, respectively. This together with our previously described isolation of elisabethatriene as the sole diterpene cyclase product in P. elisabethae suggests that the amphilectane and serrulatane families of diterpenes are derived from the same geranylgeranyl diphosphate cyclase product.     

New premyrsinane-type diterpene polyesters from Euphorbia falcata

Four new premyrsinane-type diterpenes (1-4) were isolated from the methanol extract of the whole, undried plant of Euphorbia falcata. Their structures were determined by a combination of 1D and 2D NMR (COSY, HMBC, HSQC and NOESY) techniques and mass spectral data as di-, tetra-, penta- and hexaesters of diterpene polyols, esterified with acetic, benzoic, propanoic, isobutanoic and n-hexanoic acids. One of the compounds contains a rare hemiacetal moiety. This type of diterpenes was previously detected only in four Euphorbia species (Euphorbia aleppica, Euphorbia decipiens, Euphorbia macroclada and Euphorbia pithyusa subsp. cupani).     

A novel 29-nor-3,4-seco-friedelane triterpene and a new guaiane sesquiterpene from the roots of Phyllanthus oxyphyllus

An unusual 29-nor-3,4-seco-friedelan-4(23),20(30)-dien-3-oic acid and a new 5-hydroxy-6,9-epoxyguaiane have been isolated along with other rare terpenes and lignans from Phyllanthus oxyphyllus roots. Their structures were elucidated from spectroscopic data. The radical scavenging properties of some of these compounds were evaluated. seco-Isolariciresinol showed strong antioxidant activity (IC₅₀ 0.017±0.001 mM).     

Sesquiterpenoids from Ligularia virgaurea spp. oligocephala

Four novel eremophilane-type sesquiterpene lactones, 6β,10α-dihydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (1), 6β-acetyl-2-oxoeremophila-1(10),7(11), 8(9)-trien-12,8-olide (2), 6β,8β-diacetyl-2-oxoeremophila-1(10),7(11)-dien-12,8-olide (3), dimeric eremophilane ligulolide B (5), and known sesquiterpenoid, 6β,8α-diacetyleremophila-1(10),7(11)-dien-12,8-olide (4), were isolated from an extract of the whole plant of Ligularia virgaurea spp. oligocephala. The structure of 1 was confirmed by NMR spectra and single crystal X-ray crystallography investigation, as well as 2, 3, and 5 were elucidated by spectroscopic methods including 1D and 2D NMR spectra. A discussion of biogenesis of 5 was described. Cytotoxicities of compound 1 were measured in vitro against selected cancer cells human promyelocytic leukemia (HL-60), human ovarian (HO-8910) and human lung epithehial (A-549).