Methods of Lysergic Acid Synthesis—The Key Ergot Alkaloid

Ergot is the spore form of the fungus Claviceps purpurea. Ergot alkaloids are indole compounds that are biosynthetically derived from L-tryptophan and represent the largest group of fungal nitrogen metabolites found in nature. The common part of ergot alkaloids is lysergic acid. This review shows the importance of lysergic acid as a representative of ergot alkaloids. The subject of ergot and its alkaloids is presented, with a particular focus on lysergic acid. All methods of total lysergic acid synthesis—through Woodward, Hendrickson, and Szantay intermediates and Heck coupling methods—are presented. The topic of biosynthesis is also discussed.     

The first step of biodiesel autoxidation by differential scanning calorimetry and DFT calculations

The radical abstraction reaction of (bis)-allylic hydrogen in biodiesel fatty acid chains is the first step of autoxidation, being the rate-determining one. Some intrinsic features of the intermediary radicals can determine the oxidative stability (OS) under thermodynamic control. In the present study, some common fatty acid methyl esters present in biodiesel (stearate, oleate, ricinoleate, and linoleate) were oxidized in non-isothermal conditions, using differential scanning calorimetry, and the results were compared with quantum chemical calculations at the density functional theory level. The OS order (saturated > monounsaturated > polyunsaturated) was observed in both approaches (experimental and theoretical). A slight deviation observed between oleate and ricinoleate OS’s was explained based on their allylic radicals resonance and the influence of vicinal hydroxyl group. A linear relationship was found between oxidation temperature by pressurized differential scanning calorimetry and the calculated bond dissociation energy (C–H) for the first step of autoxidation.     

双花千里光花精油的GC-MS分析

采用气相色谱-质谱联用技术对西藏药用植物双花千里光的花精油进行化学成分分析,共分离出100余个峰,鉴定出其中73个化合物,其含量占精油总量的89％以上。该花精油的成分主要为单萜、倍半萜和脂肪酸及其酯,其中大于2％的成分共有12个,占精油总量的约70％。     

Epoxidation of unsaturated FAMEs obtained from vegetable source over Ti(IV)-grafted silica catalysts: A comparison between ordered and non-ordered mesoporous materials

The liquid-phase epoxidation of mixtures of fatty acid methyl esters (FAMEs) over titanium-containing silica materials, using tert-butylhydroperoxide (TBHP) as oxidant, is here reported. The mixtures were obtained from vegetable renewable source, i.e. from high-oleic sunflower oil, coriander oil, castor oil and soya-bean oil. The influence of the nature and the position of functional groups on the C-18 chain of the FAMEs was studied. Very high activity and selectivity were obtained in the epoxidation of castor and soya-bean oil methyl esters in a reaction medium free from organic acids. Ti–MCM-41 (an ordered mesoporous titanium-grafted silica) displayed in this case, for the first time, superior performances, from a synthetic point of view, with respect to non-ordered mesoporous titanosilicates.     

Fate of the benzene hydrogens in ergot alkaloids biosynthesis

Feeding experiments with specifically labelled precursors showed that in ergot alkaloids biosynthesis, the isoprenylation of tryptophan occurs without intermediate hydroxylation.     

The synthesis of PGF1α by re-structuring of castor oil

Castor oil has been transformed—via methyl ricinoleate—to PGF₁α by strategy wherein 16 of the 18 carbons of the castor oil backbone are incorporated in the C-20 PGF₁α, involving, inter alia, a novel procedure for the regiospecific functionalisation of terminal olefins, a novel degradation of aldehyde to lower acid and strategies useful for the generation of the highly functionalised prostanoid system, which specially illustrate the utility of MEM protecting group in diverse types of chemical transformations. Additionally, this work describes the preparation of synthons having potential utility and the synthesis of novel homo—PGP₁α.     

Gas chromatographic, mass spectrometric and stable carbon isotopic investigations of organic residues of plant oils and animal fats employed as illuminants in archaeological lamps from Egypt

Man's use of illuminants in lamps or as torches to extend the working day and range of environments accessible to him would have been a major technological advance in human civilisation. The most obvious evidence for this in the archaeological record comes from pottery and stone vessels showing sooting due to the use of a wick in conjunction with a lipid-based fuel or illuminant. A wide range of potential fuels would have been exploited depending upon availability and burning requirements. Reported herein are the results of chemical investigations of a number of lamps recovered from excavations of the site of Qasr Ibrim, Egypt. Gas chromatographic, mass spectrometric and stable carbon isotopic analyses of both free (solvent extractable) and 'bound'(released from solvent extracted pottery by base treatment) lipids have revealed a wide range of saturated fatty acids, hydroxy fatty acids and alpha, omega-dicarboxylic acids. Examination of the distributions of compounds and comparisons with the fatty acid compositions of modern plant oils have allowed a range of fats and oils to be recognised. Specific illuminants identified include Brassicaceae (Cruciferae) seed oil (most likely radish oil, Raphanus sativus), castor oil (from Ricinus communis), animal fat, with less diagnostic distributions and delta(13)C values being consistent with low stearic acid plant oils, such as linseed (Linum usitatissimum) or sesame (Sesamum indicum) oils. The identifications of the various oils and fats are supported by parallel investigations of illuminant residues produced by burning various oils in replica pottery lamps. The findings are entirely consistent with the classical writers including Strabo, Pliny and Theophrastrus.     

臭椿籽挥发油的化学成分分析

采用水蒸气蒸馏法对甘肃天水产的臭椿籽挥发油进行提取，挥发油得率约为2．1％(w)；用气相色谱-质谱联用技术对挥发性成分进行了分析，鉴定了43个化合物，占挥发油相对含量的96．3％；主要成分为脂肪酸及酯、脂肪烃及甾族化合物，其中含量较高的有亚油酸、油酸、蓖麻酸和蓖麻酸甲酯。     

蓖麻油—甲基丙烯酸甲酯AB交联聚合物的研究

将蓖麻油与顺丁烯二酸酐反应,合成端乙烯基蓖麻油,再与甲基丙烯酸甲酯共聚,制得了组成不同的一系列AB交联聚合物,研究了它们的动态性能、力学性能和形态结构与组成的关系.     

Determination of Fatty Acid Methyl Esters in Biodiesel Produced from Yellow Horn Oil by LC

A simple and accurate HPLC method with refractive index detection was developed to determine the main fatty acid methyl esters in biodiesel produced from yellow horn oil. Methyl linoleate, methyl linolenate, methyl arachidate, methyl stearate, methyl palmitate and methyl oleate were separated on a HIQ SIL C18W column using methanol as mobile phase. The method has good repeatability and precision, the intraday and interday RSD for both retention time and peak area was less than 3.2%. The LOD (S/N = 3) and LOQ (S/N = 9) were less than 0.004 and 0.015 mg mL⁻¹, respectively.     

Analytical Characterization of Fatty Acids Composition of Datura alba Seed Oil by Gas Chromatography Mass Spectrometry

Methyl ester derivatives of fatty acids were analyzed for the determination of the constituents of Datura alba seed oil. Gas chromatography coupled to mass spectrometer was used for these analyses. Results delivered that there were saturated as well as unsaturated fatty acids in Datura alba seed oil. Total of 15 different fatty acid components were identified and quantified. Methyl linoleate was found in highest concentration (16.22%) among the identified analytes of interest. In addition methyl esters of Palmitic acid (6.59%), Oleic acid (5.41%) and Stearic acid (1.35%) were found. Concentrations of rest of the detected fatty acids were less than 1%. From the literature it appears that no such work has been performed for the determination of fatty acids in Datura alba seed oil.     

Synthesis of trans-10-hydroxydec-2-enoic acid and related compounds

Syntheses of the two stereoisomeric 10-hydroxydec-2-enoic acids are described. The trans-isomer is identical with the main fatty acid isolated from royal jelly of honeybees.

Some compounds closely related to this trans-acid have also been prepared.

A convenient process for the preparation of 10-acetoxy-decanoic acid from castor oil has been developed.     

On the mechanism and synthetic applications of the thermal and alkaline degradation of c-18 castor oil

The C-18 backbone of castor oil fragments, thermally to C-11 + C-7 by a π²s + π²s + o²s process and with hot alkali to c-10 + c-8 via unique sequence involving a primary reaction which is associated with three different types of redox systems as well as with uncoupled oxidation, the overall change amounting to a milieu of hydride transfer, π -migration, retro-Michael, retro-aldol, Meerwein-Pondorff-Verley as well as Cannizzaro type of reactions. These findings which constitute the core of the present work, are of significance, not only with respect to the understanding of two of the most important reactions of castor oil, but also in the utilization of this knowledge to channelize and optimize the products desired. Further, they add a distinct facet to mechanistic organic chemistry. Convincing evidence for the concerted nature of the C-18→ C-ll + C-7 change of castor oil is the clean transformation of methyl 12-hydroxy octadec 9- ynoate to the novel and useful allenic ester, methyl undeca 9,10- dienoate. Model studies with diversely α-substituted γδ-unsaturated alcohols have shown that the π²s+ σ²s + σ²s (retroene) process is assisted by a Cβ←Cα polarization. The utility of the retro-ene reaction of γδ -unsaturated alcohols has been demonstrated with a novel procedure for the PhCHO→ PhCOD change. The mechanism proposed in the present work for +he C-l8 → C-10 + C-8 change of castor oil with hot alkali provides a rationale for the formation of products at diverse redox levels. In the present work, the mechanism of the complex processes associated with the hot alkali fragmentation of castor oil has been probed using “castor soap”, a standard recipe for which has been developed. Neat castor soap decomposes above 240° to give, hydrogen gas (:), 2-octanol (49%), 2-octanone (24%) and sebacic acid (12%). A very noteworthy finding was that the course of the above can be changed by the addition of external redox acceptors whereby the formation of 2-octanol and hydrogen are suppressed. Thus, non-enolizable ketones are reduced with cast or soap [tetraphenylcyclopentadienone → tetraphenylcyclopentadiene (12%) + tetraphenylcyclopentadienone (35%); fluorenone → fluorene (34%); benzophenone → benzhydrol (44%)], hydrazones are converted to hydrocarbons [ fluorenone hydrazone → fluorene (70%); benzophenone hydrazone → diphenylmethane (50%)]and, even with calculated quantities of castor soap, amounting to the required 6e transfer, excellent yields (81-95%) of aromatic amines were obtained from a variety of aromatic nitro compounds. The easily available castor soap has good practical potential. Additionally, the delineation of the multifacetted pathways associated with the castor oil → sebacic acid change with hot alkali could be used to advantage to optimize conditions relating to products at diverse redox levels, the redox partners could be changed and the theme of co-existence of several redox systems could be transplanted to other substrates     

Labelling of castor oil for myocardial study

The labelling of castor oil, hydrolyzed castor oil and oleic acid by iodine monochloride and chloramine-T has been investigated. The effect of iodinating agent and concentration of castor oil on labelling yield has been studied. A comparative pharmacological study with analogous aliphatic fatty acids was caried out. Castor oil labelled with iodine monochloride concentrates in heart and liver in good proportion, better than other natural fatty acids and nearly equal to analogous fatty acids. Infrared study revealed that the OH group in ricinoleic acid may protect the¹²⁵I added across the double bond with minor changes in biochemical properties and better extraction by the muscle of the heart.     

Electron-transfer oxidation properties of unsaturated fatty acids and mechanistic insight into lipoxygenases

Rate constants of photoinduced electron-transfer oxidation of unsaturated fatty acids with a series of singlet excited states of oxidants in acetonitrile at 298 K were examined and the resulting electron-transfer rate constants (k(et)) were evaluated in light of the free energy relationship of electron transfer to determine the one-electron oxidation potentials (E(ox)) of unsaturated fatty acids and the intrinsic barrier of electron transfer. The k(et) values of linoleic acid with a series of oxidants are the same as the corresponding k(et) values of methyl linoleate, linolenic acid, and arachidonic acid, leading to the same E(ox) value of linoleic acid, methyl linoleate, linolenic acid, and arachidonic acid (1.76 V vs SCE), which is significantly lower than that of oleic acid (2.03 V vs SCE) as indicated by the smaller k(et) values of oleic acid than those of other unsaturated fatty acids. The radical cation of linoleic acid produced in photoinduced electron transfer from linoleic acid to the singlet excited state of 10-methylacridinium ion as well as that of 9,10-dicyanoanthracene was detected by laser flash photolysis experiments. The apparent rate constant of deprotonation of the radical cation of linoleic acid was determined as 8.1 x 10(3) s(-1). In the presence of oxygen, the addition of oxygen to the deprotonated radical produces the peroxyl radical, which has successfully been detected by ESR. No thermal electron transfer or proton-coupled electron transfer has occurred from linoleic acid to a strong one-electron oxidant, Ru(bpy)3(3+) (bpy = 2,2'-bipyridine) or Fe(bpy)3(3+). The present results on the electron-transfer and proton-transfer properties of unsaturated fatty acids provide valuable mechanistic insight into lipoxygenases to clarify the proton-coupled electron-transfer process in the catalytic function.     

Synthetic Route to Ergot Alkaloids

Rye is sometimes infected by a fungus called Claviceps purpurea. The term ergot designates the dark, brown, tuberous bodies which can be collected before or during harvesting and represent one of the most remarkable drugs of our therapeutic arsenal. Actually, the most significant alkaloids are metabolic products of these fungi. We elaborated three alternative total synthetic pathways to construct the ergoline skeleton, one of which – suitable for scaling up – finally resulted in (+)‐lysergic acid ( 32a ) and α‐ergocryptine ( 1 ) (Schemes 5 and 6).     

Quantitative analysis of fatty acid methyl esters and dimethyl acetals on a polar (free fatty acid phase) capillary column

Separation of fatty acid methyl esters and dimethyl acetals from complex biological samples has been achieved by gas-liquid chromatography on a capillary column coated with free fatty acid phase. Response-correcting factors were determined, showing rather large variations with fatty acid length. Polyunsaturated fatty acid methyl esters were shown to have lower responses than saturated species, whereas dimethyl acetals and equivalent methyl esters were found to give similar responses. Total fatty acid and aldehyde compositions of human and simian erythrocytes were determined and compared, showing a somewhat higher level of linoleate and arachidonate, and a lower level of plasmalogens in simian erythrocytes.     

Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii,a Mutualistic Fungus of French Guiana Termites

Social insects are in mutualism with microorganisms, contributing to their resistance against infectious diseases. The fungus Pseudallescheria boydii SNB-CN85 isolated from termites produces ovalicin derivatives resulting from the esterification of the less hindered site of the ovalicin epoxide by long-chain fatty acids. Their structures were elucidated using spectroscopic analysis and semisynthesis from ovalicin. For ovalicin, these compounds displayed antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei, with IC₅₀ values of 19.8 and 1.1 µM, respectively, for the most active compound, i.e., ovalicin linoleate. In parallel, metabolomic profiling of a collection of P. boydii strains associated with termites made it possible to highlight this class of compounds together with tyroscherin derivatives in all strains. Finally, the complete genome of P. boydii strains was obtained by sequencing, and the cluster of potential ovalicin and ovalicin biosynthesis genes was annotated. Through these metabolomic and genomic analyses, a new ovalicin derivative named boyden C, in which the 6-membered ring of ovalicin was opened by oxidative cleavage, was isolated and structurally characterized.     

Stereochemistry of a bifunctional dihydroceramide delta 4-desaturase/hydroxylase from Candida albicans; a key enzyme of sphingolipid metabolism

The stereochemical course of the dihydroceramide delta 4-(E)-desaturase from Candida albicans, cloned and expressed in the yeast Saccharomyces cerevisiae strain sur2 delta, was determined using stereospecifically labelled (2R,3S)-[2,3,4,4-2H4]-palmitic acid as a metabolic probe. Mass spectrometric analysis of the dinitrophenyl-derivatives of the labelled long-chain bases revealed elimination of a single deuterium atom from C(4) (corresponding to the C(4)-HR) along with a hydrogen atom from C(5) (corresponding to the C(5)-HS). This finding is consistent with an overall syn-elimination of the two vicinal hydrogen atoms. Besides the desaturation product sphingosine (93%) minor amounts of a 4-hydroxylated product (phytosphinganine, 7%) were identified that classify the Candida enzyme as a bifunctional desaturase/hydroxylase. Both processes, desaturation and hydroxylation proceed with loss of C(4)-HR from the chiral precursor. This finding is in agreement with a two-step process involving activation of the substrate by removal of the C(4)-HR to give a C-centred radical or radicaloid followed by either disproportionation into an olefin, water and a reduced diiron complex, or to recombination of the primary reactive intermediate with an active site-bound oxygen to yield a secondary alcohol. This result demonstrates the close mechanistic relationship between desaturation and hydroxylation as two different reaction pathways of a single enzyme and strengthens the mechanistic relationship of desaturases from fatty acid metabolism and sphingolipids.