Chemical Review of Gorgostane-Type Steroids Isolated from Marine Organisms and Their 13C-NMR Spectroscopic Data Characteristics.

Gorgostane steroids are isolated from marine organisms and consist of 30 carbon atoms with a characteristic cyclopropane moiety. From the pioneering results to the end of 2021, isolation, biosynthesis, and structural elucidation using 13C-NMR will be used. Overall, 75 compounds are categorized into five major groups: gorgost-5-ene, 5,6-epoxygorgostane, 5,6-dihydroxygorgostane, 9,11-secogorgostane, and 23-demethylgorgostane, in addition to miscellaneous gorgostane. The structural diversity, selectivity for marine organisms, and biological effects of gorgostane steroids have generated considerable interest in the field of drug discovery research.

LC-MS analysis of oils of Monodora myristica and Monodora tenuifolia and isolation of a novel cyclopropane fatty acid.

Seeds of Monodora myristica and M. tenuifolia were extracted with hexane and the extracts were subjected to column chromatography, LC-MS and NMR analysis. In addition to masses of previously isolated compounds, other masses corresponding to unidentified compounds from the plants were detected. Using 2 D NMR techniques, one of the fractions from M. tenuifolia was characterised as a novel 13-(2-butylcyclopropyl)-6,9-dodecadienoic acid. However, none of the compounds detected in LC-MS corresponded to the ones previously identified by GC-MS.

Bioanalytical technique for determination of tasimelteon in human plasma by LC-MS/MS and its application to pharmacokinetic study in humans.

A highly sensitive, specific and rapid liquid chromatography-tandem mass spectrometry technique for the quantification of tasimelteon in human plasma has been developed and validated using tasimelteon-d5 as internal standard. Liquid-liquid extraction technique with ethyl acetate was used for extraction of tasimelteon from the plasma. The chromatographic separation was achieved on an Agilent Zorbax, Eclipse, C18 (4.6 × 50 mm, 5 µm) column using a mobile phase of acetonitrile and 0.02% formic acid buffer (85:15, v/v) with a flow rate of 0.5 mL/min. A detailed method validation was performed as per the United States Food and Drug Administration guidelines. The linear calibration curve was obtained over the concentration range 0.30-299 ng/mL. The API-4000 liquid chromatography-tandem mass spectrometry was operated under multiple reaction monitoring mode during analysis. The validated method was successfully applied to estimate plasma concentration of tasimelteon after oral administration of a single dose of a 20 mg capsule in healthy volunteers under fasting conditions. The maximum concentration of the drug achieved in the plasma was 314 ± 147 ng/mL and the time at which this concentration was attained was 0.54 ± 0.22 h.

Separation of structurally related primary aliphatic amines using hydrophilic interaction chromatography with fluorescence detection after postcolumn derivatization with o-phthaldialdehyde/mercaptoethanol.

The retention behavior of primary aliphatic amines (homologous series of aliphatic alkyl amines and cycloalkyl amines) and positional isomers of alkylamines in the hydrophilic interaction chromatography mode was studied. The study was carried out on a TSKgel Amide-80 column followed by postcolumn derivatization with fluorescence detection to describe the retention mechanism of tested compounds. The effect of chromatographic conditions including column temperature, acetonitrile content in the mobile phase, mobile phase pH (ranging from 3.5 to 6.8), and salt concentration in the mobile phase was investigated. The final mobile phase consisted of acetonitrile and solution of 20 mM potassium formate pH 3.5 in ratio 80:20 v/v. The analyses were carried out at mobile phase flow rate of 1.0 mL/min and the column temperature of 20°C. The developed method was fully validated in terms of linearity, sensitivity (limit of detection and limit of quantification), accuracy, and precision according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. The proposed new methods were proved to be highly sensitive, simple, and rapid, and were successfully applied to the determinations of isopropylamine, cyclohexylamine, and cyclopropylamine in relevant active pharmaceutical ingredients.

Cyclohelminthol X, a Hexa-Substituted Spirocyclopropane from Helminthosporium velutinum yone96: Structural Elucidation, Electronic Circular Dichroism Analysis, and Biological Properties.

Helminthosporium velutinum yone96 produces cyclohelminthol X (1), a unique hexa-substituted spirocyclopropane. Although its molecular formula and NMR spectral data resemble those of AD0157, being isolated from marine fungus Paraconiothyrium sp. HL-78-gCHSP3-B005, our detailed analyses disclosed a totally different structure. Chemical shift calculations and electronic circular dichroism spectral calculations were quite helpful to establish the structure, when those were performed based on density functional theory. The carbon framework of cyclohelminthols I-IV is found at the C1-C8 propenylcyclopentene substructure of 1. Thus, 1 is assumed to be biosynthesized by cyclopropanation between an oxidized form of cyclohelminthol IV and a succinic anhydride derivative 4. Cytotoxicity for two cancer cell lines and proteasome inhibition efficiency are measured.

Curacin E from the Brittle Star Ophiocoma scolopendrina.

Bioassay-guided fractionation of the extract of the brittle star Ophiocoma scolopendrina afforded curacin E (1), a congener of curacin A (2). Curacin A (2) is an antimitotic agent of cyanobacterial origin. The structure of curacin E was studied by interpretation of NMR data and the ECD spectrum. Curacin E has an ethylcarbonyl terminus in its side chain and inhibits the proliferation of P388 cells.

UPLC-MSE profiling of Phytoplankton metabolites: application to the identification of pigments and structural analysis of metabolites in Porphyridium purpureum.

A fast and high-resolution UPLC-MSE analysis was used to identify phytoplankton pigments in an ethanol extract of Porphyridium purpureum (Pp) devoid of phycobiliproteins. In a first step, 22 standard pigments were analyzed by UPLC-MSE to build a database including retention time and accurate masses of parent and fragment ions. Using this database, seven pigments or derivatives previously reported in Pp were unequivocally identified: ß,ß-carotene, chlorophyll a, zeaxanthin, chlorophyllide a, pheophorbide a, pheophytin a, and cryptoxanthin. Minor amounts of Divinyl chlorophyll a, a chemotaxonomic pigment marker for prochlorophytes, were also unequivocally identified using the database. Additional analysis of ionization and fragmentation patterns indicated the presence of ions that could correspond to hydroxylated derivatives of chlorophyll a and pheophytin a, produced during the ethanolic extraction, as well as previously described galactosyldiacylglycerols, the thylakoid coenzyme plastoquinone, and gracilamide B, a molecule previously reported in the red seaweed Gracillaria asiatica. These data point to UPLC-MSE as an efficient technique to identify phytoplankton pigments for which standards are available, and demonstrate its major interest as a complementary method for the structural elucidation of ionizable marine molecules.

Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators.

Covering: 1973 to 2013. The biological activities of tigliane, lathyrane, ingenane, casbane, jatropholane and premyrsinane diterpenoids which contain the gem-dimethylcyclopropyl unit are described. Particular attention is given to their anti-viral, anti-microbial and cytotoxic activities. In the main text there are 132 references. The electronic supplementary information contains tables listing 424 of these diterpenoids, their occurrence and biological activity together with the references.

HPTLC and reverse phase HPLC methods for the simultaneous quantification and in vitro screening of antioxidant potential of isolated sesquiterpenoids from the rhizomes of Cyperus rotundus.

Three sesquiterpenoids solavetivone, aristolone and nootkatone were isolated from the acetone extract of Cyperus rotundus by silica gel column chromatography and identified by spectral studies. Solavetivone has been isolated for the first time from the species. Simple, sensitive and selective HPTLC and HPLC methods with ultraviolet detection (245 nm) were developed and validated for the simultaneous quantification. HPTLC method was validated in terms of their linearity, LOD, LOQ, precision, accuracy and compared with RP-HPLC-UV method. Among the three sesquiterpenoids isolated, nootkatone possessed the highest radical scavenging potential (IC(50) 4.81 µg/ml) followed by aristolone (IC(50) 5.28 µg/ml) and solavetivone (IC(50) 6.82 µg/ml) by DPPH radical scavenging assay. Total antioxidant activity against phosphomolybdenum reagent was also studied. The methods described in this paper were able to identify and quantify sesquiterpenoids from the complex mixtures of phytochemicals and could be extended to the marker based standardization of polyherbal formulations containing C. rotundus.

Cyclopropane- and spirolimonoids and related compounds from Hortia oreadica.

The dichloromethane extract from taproots of Hortia oreadica afforded six limonoids, these are 9,11-dehydro-12α-acetoxyhortiolide A, hortiolide C, 11α-acetoxy-15-deoxy-6-hydroxyhortiolide C, hortiolide D, hortiolide E, 12ß-hydroxyhortiolide E, in addition to the known limonoid, guyanin. The dichloromethane extract from stems of H. oreadica also afforded two limonoids 9,11-dehydro-12α-hydroxyhortiolide A and 6-hydroxyhortiolide C. As a result of this study and literature data, Hortia has been shown to produce highly specialized limonoids that are similar to those from the Flindersia (Flindersioideae). The taxonomy of Hortia has been debatable, with most authors placing it in the Toddalioideae. Considering the complexity of the isolated limonoids, Hortia does not show any close affinity to the genera of Toddalioideae. That is, the limonoids appear to be of little value in resolving the taxonomic situation of Hortia.

Isolation of C11 compounds and a cyclopropane fatty acid from an Okinawan ascidian, Diplosoma sp.

Pentylphenols 1 and 2, cyclopropane fatty acid 3, and cyclopentenones 4 and 5, were isolated from an ascidian, Diplosoma sp. The structures of 1-5 were determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity against HCT116 cells (human colorectal cancer cell).

Diplonine, a neurotoxin isolated from cultures of the fungus Stenocarpella maydis (Berk.) Sacc. that induces diplodiosis.

Diplodiosis is a neuromycotoxicosis of cattle and sheep caused by ingestion of maize infected with the ear-rot fungus Stenocarpella (= Diplodia ) maydis . Apart from ataxia, paresis, and paralysis, the toxin is responsible for stillbirths and neonatal losses characterized by the presence of spongiform degeneration in the white matter of the brain in the offspring of dams exposed to infected maize cobs. In the present study a toxin, named diplonine, which induced neurological signs in guinea pigs resembling some of those occurring in cattle and sheep, was isolated from S. maydis cultures. Purification of diplonine was achieved by methanol extraction followed by chromatographic separation on silica gel and RP-18 stationary phases. The structure and relative configuration of diplonine were defined by analysis of NMR and MS data as (S)-2-amino-2-[(1R,2S)-1-hydroxy-2-methylcyclopropyl]acetic acid or the (S)-2-amino-2-[(1S,2R)-diastereomer.

Identification of the toxic trigger in mushroom poisoning.

We have isolated the small, highly strained carboxylic acid cycloprop-2-ene carboxylic acid from the Asian toxic mushroom Russula subnigricans. This compound is responsible for fatal rhabdomyolysis, a new type of mushroom poisoning that is indicated by an increase in serum creatine phosphokinase activity in mice. We found that polymerization of the compound at high concentrations via ene reaction abolishes its toxicity.

The chiral pyrethroid cycloprothrin: stereoisomer synthesis and separation and stereoselective insecticidal activity.

The synthesis and separation of the isomers of the pesticide cycloprothrin have been realized for the first time. Complete separation was achieved on a DAICEL CHIRALCEL OJ-H column (25 x 0.46 cm) for (1R, alpha*)-cycloprothrin isomers and on a DAICEL CHIRALCEL OD-H column (25 x 0.46 cm()) for (1S, alpha*)-cycloprothrin isomers. The insecticidal activity of (1R, alphaR)-cycloprothrin for the larvae of Mythimaseparata and Aphismedicagini was found to be about six times and four times higher, respectively, than that of racemic cycloprothrin.

Chiral HPLC analysis of milnacipran and its FMOC-derivative on cellulose-based stationary phases.

The HPLC enantioseparation of the last generation antidepressive drug milnacipran (+/-)-1 was investigated on different cellulose-based chiral stationary phases (CSPs). On carbamate-type columns, Chiralcel OD and OD-H (+/-)-1 could be separated with alpha value about 1.20 but the resolution was quite low because of the tailing of the peaks. Direct determination of (+/-)-1 with high selectivity and resolution was obtained on Chiralcel OJ in normal phase mode elution. Precolumn derivatization of milnacipran with Fmoc-Cl gave compound (+/-)-2 which was enantioseparated on all the investigated CSPs and allowed enhanced UV or fluorimetric detection. The Chiralpak IB, that could be considered the immobilized version of Chiralcel OD-H, was found completely ineffective in the chiral recognition of (+/-)-1 and moderately efficient in the separation of (+/-)-2.

Release of 1-methylcyclopropene from heat-pressed polymer films.

Gaseous 1-methylcyclopropene (1-MCP) is an inhibitor of ethylene perception that is being used extensively for apples and ornamental products, and under intensive investigation for its potential benefits for other fruits and vegetables. 1-MCP is currently used in closed environments that maintain stable concentrations for several hours in order to be effective. However, food packaging materials that release 1-MCP at a predictable rate into the package headspace might be useful for application in inhibiting the deleterious effects of ethylene in the postharvest packaging and storage of some horticultural products. A 1-MCP/alpha-cyclodextrin (1-MCP-cd) complex was incorporated into several common packaging films by heat-pressing (dry-blend, lamination) and solution-casting methods. The release of 1-MCP from the films was quantified by gas chromatography with respect to time, loading of 1-MCP, temperature, relative humidity (RH), type of film, and film-forming method. Release of 1-MCP was rapid and high in films held at RH >/= 75%. The rate of release was slow during the 1st 12 h and then increased during the next 24 to 36 h. Higher temperatures resulted in higher and faster release. A loading of 8 mg of 1-MCP-cd per 140 mg of polymer was found to be optimal. Pressing 1-MCP-cd containing films above 100 degrees C reduced the amount of 1-MCP remaining in the film. Incorporation into LDPE resulted in a higher and faster release than from PS, PVC, and PP polymers. 1-MCP release from a film matrix appears to be within the acceptable range for produce packaging applications.

Novel cyclopropane fatty acids from the phospholipids of the Caribbean sponge Pseudospongosorites suberitoides.

The cyclopropane fatty acids 17-methyl-trans-4,5-methyleneoctadecanoic acid, 18-methyl-trans-4,5-methylenenonadecanoic acid, and 17-methyl-trans-4,5-methylenenonadecanoic acid were characterized for the first time in nature in the phospholipids (mainly PE, PG and PS) of the hermit-crab sponge Pseudospongosorites suberitoides. Pyrrolidine derivatization was the key in identifying the position of the cyclopropyl and methyl groups in the acyl chains and (1)H NMR was used to determine the trans stereochemistry of the cyclopropane ring. The phospholipids from the sponge also contained an interesting series of iso-anteiso Delta(5,9) fatty acids with chain-lengths between 17 and 21 carbons, with the fatty acids (5Z,9Z)-18-methyl-5,9-nonadecadienoic acid and the (5Z,9Z)-17-methyl-5,9-nonadecadienoic acid being described for the first time in sponges. The anteiso alpha-methoxylated fatty acid 2-methoxy-12-methyltetradecanoic acid was also identified for the first time in nature in the phospholipids of this interesting marine sponge. The novel cyclopropyl fatty acids could have originated from the phospholipids of a cyanobacterium living in symbiosis with the sponge.

Enantioseparation and determination of 2,2-dimethylcyclopropanecarboxamide and corresponding acid in the bioconversion broth by gas chromatography.

A simple and sensitive method employing gas chromatography was developed for the enantioseparation and determination of 2,2-dimethylcyclopropanecarboxamide and its acid in the bioconversion broth. Samples were recovered in high yield by extracting the broth with equal volumes of ethyl acetate twice. Separation of the four enantiomers was performed on a gamma-cyclodextrin based chiral column BGB-175. The effect of column flow rate and temperature on the retention and resolution of the enantiomers was investigated. The proposed method exhibited good linearity, repeatability and precision, and was successfully used to monitor and control the bioconversion process of 2,2-dimethylcyclopropanecarboxamide.

Gracilarioside and gracilamides from the red alga Gracilaria asiatica.

One gracilarioside and two gracilamides with unusual cyclopropane-containing alkyl chains were isolated from the red alga Gracilaria asiatica. Their structures were determined by spectroscopic methods and microscale chemical degradation. To our knowledge, no ceramides with a cyclopropane ring have been reported from marine organisms. These three compounds were mildly cytotoxic to the human A375-S2 melanoma cell line.

Cyclopropenylidenes: from interstellar space to an isolated derivative in the laboratory.

Like many of the molecular species that have been detected in the interstellar medium, the singlet carbene cyclopropenylidene (C3H2) has been presumed to be too unstable to isolate in the laboratory. However, by appending pi-electron-donating amino groups to the triangular skeleton, we prepared a cyclopropenylidene derivative that is stable at room temperature. In contrast to previously isolated carbenes, this compound does not require a heteroatom adjacent to the electron-deficient carbon to confer stability. Despite the presence of amino groups, the geometric parameters of the cyclic skeleton, revealed by x-ray crystallography, are only slightly perturbed relative to those of the calculated structure of unsubstituted cyclopropenylidene. Stable cyclopropenylidene derivatives might thus serve as models for a better understanding of the formation of carbon-bearing molecules in the interstellar medium.