Application of Lawesson’s reagent in the synthesis of sulfur-containing medicinally significant natural alkaloids

This review aims to illustrate the applications of Lawesson's reagent (LR) [2,4-bis(p-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide] in the synthesis of naturally occurring medicinally important alkaloids. LR is primarily used for thionation; it is a versatile reagent employed for diverse transformations (cyclizations, rearrangements, and synthesis of heterocyclic compounds). The medicinal importance of alkaloids has also been concisely highlighted. The main focus of the review is the use of LR in the synthesis of natural alkaloids and only the thionation steps involved have been highlighted.     

High-yield diacylglycerol formation by solid-phase enzymatic glycerolysis of hydrogenated beef tallow

Diglyceride (DG) was prepared by reaction of hydrogenated beef tallow and glycerol in the presence of aPsesudomonas lipase. The yield of DG depended strongly on the reaction temperature. After initial incubation at 60°C for 2 h, followed by the first temperature shift down to 55°C for 4 h and then the second shift down to 48°C for up to 3 d, the reaction mixture became solid and a yield of approximately 90% DG was obtained. About 95% of total DG was 1,3-DG. The yield of DG was also dependent on the glycerol (GL) to triglyceride (TG) molar ratio. At the molar ratio of 1∶2 (GL/TG), the enzyme-catalyzed reaction was highly efficient and utilized essentially all of the glycerol. The free fatty acid (FFA) content at equilibrium depended on the water concentration in the glycerol phase. The initial rate of FFA formation was low and was hardly affected by the moisture content between 0.5 and 4%, but, at higher water content (4–6.7%), there was a small increase in the rate.     

Improved HPLC assay for lipid peroxides in human plasma using the internal standard of hydroperoxide

We have developed a sensitive reversed-phase chemiluminescence HPLC approach for simultaneous quantitative and qualitative analyses of hydroperoxides of cholesteryl ester and TC in human plasma. Standard hydroperoxides of cholesteryl ester and TG and a novel internal standard (1-tetradecanyl 3-octadecenoyloxy-5β-cholan-24-oate monohydroperoxide) (I.S.) were chemically synthesized and the standard curves confirmed to be linear throughout the calibration range (1–1000 pmol). Within-day and between-day CV were less than 7%, and the recoveries were within the range of 84–93%. With sample size minimized to 0.1 mL of plasma for each run, plasma cholesteryl ester hydroperoxide levels were 189±87 nM (mean±SD) in healthy young (22–25 yr old; n=15, male/female=6∶9) and 210 ±69 nM in healthy elderly (39–60 yr old; n=6, male/female= 3∶3). TG hydroperoxide was not detected in healthy subjects. In patients with advanced liver failure (36–67 yr old; n=4, male/female=2∶2), hydroperoxide levels of plasma cholesteryl ester and TG were 11,903±9,553 nM and 3,318±1,590 nM, respectively, indicating an involvement of lipid oxidation. Sensitive and specific monitoring of plasma lipid peroxides using the present chemiluminescence HPLC approach with the synthesized I.S. may help our understanding of chemical and pathophysiological aspects of lipid peroxidation.     

Production of 8,11,14,17-cis-eicosatetraenoic acid by Δ5 desaturase-defective mutants of an arachidonic acid-producing fungus, Mortierella alpina

Δ5 Desaturase-defective mutants of an arachidonic acid-producing fungus, Mortierella alpina 1S-4, accumulate large amounts of 8,11,14,17-cis-eicosatetraenoic acid (20:4ω3) when grown with linseed oil. One of the mutants, the S14 strain, produced 1.65 mg of 20:4ω3 per mL of culture medium (corresponding to 66.0 mg/g dry mycelia and 11.6% of total cellular fatty acids) when grown in a medium containing 1% glucose, 1% yeast extract, and 4% linseed oil methyl ester at 28°C for 2 d, and then at 16°C for 7 d. In a bench-scale fermentation in a 5-L jar fermenter, 20:4ω3 production reached 1.60 g/L of culture medium on the eighth day (corresponding to 77.3 mg/g dry mycelia and 26.0% of total cellular fatty acids). The cellular lipids of the S14 strain comprised 75.8% triacylglycerol (TG), 6.7% diacylglycerol, and 13.3% phospholipids (PL). The percentage of 20:4ω3 was higher in PL than in TG, and highest in phosphatidylcholine (32.6%).     

Enzymatic preparation of enantiomerically pure sn-2,3-diacylglycerols: A stereoselective ethanolysis approach

Stereoselective ethanolysis of monoacid TAG by immobilized Rhizomucor miehei lipase (RML) was studied for preparation of optically pure sn-2,3-DAG. Trioctanoylglycerol (TO) was used as a model substrate. The enantiomeric purity of the product, sn-2,3-dioctanoylglycerol (sn-2,3-DO), was very high (percent enantiomeric excess >99%) when an excess of ethanol was used. The result indicated that RML was highly stereoselective toward the sn-1 position of TO under conditions of excess ethanol. The stereoselectivity of RML depended on the amount of ethanol. The larger the amount of ethanol was, the higher the stereoselectivity became. After optimizing the parameters such as reactant molar ratio, water content, and temperature, (ethanol/TO molar ratio =31∶1 and water content =7.5 wt% of the reactants at 25°C), optically pure sn-2,3-DO was obtained at 61.1 mol% in the glyceride fraction in 20 min. The above conditions were further applied for ethanolysis of monoacid TAG with different acyl groups such as tridecanoylglycerol (C10∶0), tridodecanoylglycerol (C12∶0), tritetradecanoylglycerol (C14∶0) and trioctadecenoylglycerol [triolein, (C18∶1)]. The yields and enantiomeric purities of 1,2(2,3)-DAG were dramatically reduced when TAG with FA longer than decanoic acid were used.     

Structure of peanut oil triacylglycerols from cultivars of diverse genetic background

Triacylglycerols (TG) were isolated from peanut cultivars chosen to embrace known extremes in oleic and linoleic acid content, and the TG structure were determined using pancreatic lipase hydrolysis. Molar concentrations of oleic and linoleic acid insn-2-monoacylglycerols (MG) were highly correlated with molar concentrations in TG. Correlation coefficients were 0.99 in each case. Molar concentrations of oleic and linoleic in 2-MG are given by: MG_18∶1=1.37TG_18∶1-20.8; MG_18∶2=1.71TG_18∶2+0.66. Linoleicoleic ratios ranged from 0.2–1.1 for TG, 0.2–2.6 forsn-2-MG, and 0.2–0.6 for acids in the 1(3)-positions of TG. Molar concentrations of linoleic acid in the 1(3)-positions of TG ranged from 7–26%. The linoleic-oleic ratios and molar concentrations of 1(3) linoleic acid in some cultivars were similar to values that have been reported for relatively nonatherogenic corn oil and randomized peanut oil.     

Triglyceride specificity ofCandida cylindracea lipase: Effect of docosahexaenoic acid on resistance of triglyceride to lipase

Tuna oil was hydrolyzed withCandida cylindracea lipase. After 70% hydrolysis of the oil, the docosahexaenoic acid (DHA) content in the glyceride mixture [a mixture of TG (triglyceride), DG (diglyceride) and MG (monoglyceride)] was twice that of the original oil. DHA-rich TG and DG were observed, but DHA-rich MG was absent.C. cylin-dracea lipase seemed to have a “triglyceride specificity,” and it favors TG without DHA over TG containing DHA. In accordance with this hypothesis, TG containing a mixture of oleic acid (OA) and DHA was synthesized and then hydrolyzed withC. cylindracea lipase. TGs in the hydrolysis product were fractionated and analyzed quantitatively by high-performance liquid chromatography. Four kinds of TGs were obtained. TG with three molecules of OA was hydrolyzed most easily. Increasing the DHA content of TG resulted in less hydrolysis of TG. The results suggested thatC. cylindracea lipase had a TG specificity for the whole structure of TG in preference to the individual ester bonds; OA coexisting with DHA in TG was resistant toC. cylindracea lipase due to the TG structure.     

Novel carbonaceous coupling products containing sulphur

Summary The coupling of alkali ethynides with CSCl₂, SOCl₂, or SO₂Cl₂ results in new carbonaceous polymeric products; their structures were studied by FTIR and XPS spectra, and the assumptions on reaction mechanism were made with respect to the found elemental composition and model calculations. These macromolecular products, obtained in the yields of 80–92%, contain chlorine in the chain terminals, and alkyne sequences along with inserted C=S, S=O or SO₂ groups. These inserted sulphur groups contribute to the stability of alkyne sequences as evidenced by FTIR spectra. Soluble thioketone iPr₃SiC≡C–CS–C≡CSiiPr₃ (2) prepared by similar coupling of iPr₃SiC≡CLi (1) with CSCl₂ in the yield of 72%, was considered as a support of the suggested coupling mechanism. Similarly monomolecular sulfoxide iPr₃SiC≡C–SO–C≡CSiiPr₃ (3) was prepared by coupling of iPr₃SiC≡CLi (1) with SOCl₂ in the yield 75%.     

Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans

Polyunsaturated dietary fat (n−3 and n−6) results in less atherosclerosis in monkeys compared to lard (Parks, J.S., Kaduck-Sawyer, J., Bullock, B.C., and Rudel, L.L.,Arteriosclerosis 10, 1102–1112; Rudel, L.L., Parks, J.S., Johnson, F.L., and Babiak, J.,J. Lipid Res. 27, 465–474, 1986). We hypothesized that this was due, in part, to a decreased reactivity of low density lipoproteins (LDL) with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys were fed diets containing lard, safflower oil (n−6 polyunsaturated; Poly), menhanden fish oil (FO), or oleic acid-rich safflower oil (oleinate; Mono) for 14 mon, and plasma LDL were isolated and characterized. Several properties of LDL thought to be important in the interaction of LDL with arterial PG were measured including LDL particle size, chemical composition, sialic acid content, density distribution, apolipoprotein E (apoE) content and cholesteryl ester transition temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet consumption averaged (mean±SEM): FO (366±45), Lard (352±27), Poly (279±24), and Mono (230±43). The composition of LDL was similar among diet groups except that FO LDL were relatively depleted of cholesteryl ester and enriched in protein and were smaller in size. LDL sialic acid content was similar among diet groups (4.5–5.0 μg/mg LDL protein). The LDL apoE/B molar ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0±1.0), Poly (2.0±0.1), Lard (1.8±0.5), and FO (1.0±0.2). The FO group had a lower proportion (13%) of the apoE enriched d=1.015–1.025 g/mL subfraction of LDL than did the other diet groups (31–45%). The transition temperature of the LDL cholesteryl esters was below body temperature for the FO and Poly groups (36°C) and above for the Lard and Mono groups (40–44°C). The percentage of LDL cholesterol that formed insoluble complexes with arterial chondroitin sulfate PG averaged: Mono (29±4%), Lard (18±3%), Poly (14±3%), and FO (7±2%). Among all diet groups, there was a significant positive correlation (r=0.54) between LDL-PG complex formation and LDL apoE/B molar ratio. We conclude that dietary FO and Poly result in LDL that are less reactive with arterial PG compared to Lard or Mono fats. While FO appears to decrease PG binding by decreasing the apoE content and amount of the largest LDL subfraction, Poly fat appears to affect LDL-PG interactions by other mechanisms. Decreased LDL-PG interactions may lead to decreased atherosclerosis in animals fed polyunsaturated dietary fat.     

Triacylglycerol composition of Pinus koraiensis seed oil

The triacylglycerol (TG) composition of Pinus koraiensis seed oil, which contains Δ5 nonmethylene-interrupted (NMI) fatty acids (FA) (the main acid is pinolenic, 18:3 Δ5, 9, 12), was determined. TG were preliminarily separated by argentation thin-layer chromatography (TLC), and the obtained fractions were analyzed by high-temperature gas chromatography (GC) on a capillary column with methyl phenyl silicone phase. Additionally, high-performance liquid chromatography (HPLC) of TG was applied. The FA composition of all TG fractions was identified. The identification of TG was carried out by combining TLC, GC, HPLC, and calculated equivalent carbon numbers of TG standards. The TG species identification was confirmed by comparison of the theoretical recalculated and directly analyzed FA compositions of all TLC fractions of TG. Species of TG with unsaturation degrees of 1 to 7 and trace amounts of saturated and octaenoic TG species were found. Except for minor compounds, 26 TG molecular species of 32 main components were quantitatively determined. The main species were oleoyl dilinoleoylglycerol (14.7%), dilinoleoyl pinolenoylglycerol (10.7%), palmitoyl oleoyl linoleoylglycerol (8.3%), triolein (7.6%), and dioleoyl, linoleoylglycerol (7.4%). Seven TG species contained Δ5 NMI acyl groups. Of these, the major were dilinoleoyl pinolenoyglycerol (10.7%), stearoyl linoleoyl pinolenoylglycerol (6.5%) dioleoyl, pinolenoylglycerol (5.4%), and palmitoyl linoleoyl pinolenoyl-glycerol (5.5%). TG species with two or three NMI acyl groups were not detected.     

X-Ray Diffraction,Thermal and Spectroscopic Studies on 2,4-Dinitrodiphenylamine (DNDPA)

2,4-Dinitrodiphenylamine (DNDPA) has been studied as regards its crystal structure and thermal decomposition characteristics using X-ray diffraction (XRD), simultaneous thermal analysis, ultraviolet and visible spectroscopy, infrared spectroscopy, hot-stage microscopy and high performance liquid chromatography (HPLC). The elementary cell parameters obtained from the XRD pattern are a=17.002 Å, b=17.002 Å, c=20.400 Å. The crystal structure belongs to the hexagonal system with c/a ratio 1.1999. IR spectra of 2,4-DNDPA have also been recorded and the bands assigned. Kinetics of thermolysis has been followed both by isothermal thermogravimetry (TG) and HPLC. The best linearity with a correlation coefficient of 0.994 was obtained for the two-dimensional diffusion controlled equation in TG. Activation energy was found to be 83.0 kJ/mol and log A (in s⁻¹)=6.0 from isothermal TG. The rupture of the C NH bond followed by the C NO₂ bond constitutes the primary step in the thermolysis and the decomposition is free-radical assisted.     

Acrolein Adsorption on Gold Clusters,A Theoretical Study of Conjugation Effect on C=C and C=O Interaction with Au Clusters

Abstract  

We studied acrolein (AC) adsorption on gold clusters Au _n (n = 1–5) using density functional theory. It is demonstrated that conjugation effect reduces the adsorbate–substrate interaction through π-(C=C), π-(C=O) and di-σ-(C=O) modes whereas it facilitates the di-σ-(C=C) and the σ-O configurations. Analysis reveals that in π-(C=C) and π-(C=O) modes acrolein uses the HOMO-1 orbital to interact with the clusters while in σ-O mode the HOMO of AC plays the role. For di-σ-(C=C), di-σ-(C, O) and di-(C=O), the HOMO orbital of the cluster donates electrons to acrolein. Acrolein adsorption through the C=C bond is more favorable than that via the C=O group, which explains why the yields of C=C hydrogenation is higher than that of C=O reduction.     

Study on synthesis of novel soluble aromatic polyamides with pendant cyano groups

A series of novel soluble aromatic polyamides with pendant cyano groups were synthesized by low temperature polycondensation of aromatic diamines with a new monomer 2,6-bis(4-chloroformylphenoxy)benzonitrile (ClPOBN) in the presence of N,N-dimethylacetamide (DMAC) as the solvent and tertiary amines as the absorbent of HCl. The properties and structures of obtained polymers were characterized by means of FTIR, TG, and elemental analysis. Structures of prepared polymers are as expected. TG studies show that the polymers had excellent thermal stability as measured by 5% weight loss temperatures in nitrogen (409–438 °C).They are soluble in aprotic polar organic solvents such as N-methyl pyrrolidone (NMP), dimethyl sulphoxide (DMSO) and N,N-dimethylformamides (DMF) and are swelled in common solvents, such as CHCl_3, ethylene dichloride (DCE), CH₂Cl₂, tetrahydrofuran (THF), etc. Their thin films which cast from DMF had tensile strength of 79–93 MPa, Young’s moduli of 1.7–2.6 GP, elongation at break of 9–15%, indicating they are strong in mechanical properties.     

Synthesis of highly dispersed phosphotungstic acid encapsulated in MIL-100(Fe) catalyst and its performance in heterogeneous oxidative desulfurization

Highly efficient HPW(x)/MIL-100(Fe) catalysts with different phosphotungstic acid (HPW) loading (x, wt%) were successfully synthesized by a one-step hydrothermal method and characterized by XRD, SEM, FTIR, and BET. The influences of HPW loading, catalyst dosage, temperature, and O/S molar ratio on oxidative desulfurization (ODS) were investigated. The results indicated that the HPW(x)/MIL-100(Fe) retained the structure of its parent MIL-100(Fe). The MIL-100(Fe) presented a high surface area, which is beneficial to dispersion of HPW. The HPW(x)/MIL-100(Fe) with HPW loading of 40% exhibited excellent ODS activity. At a temperature of 50?°C, a catalyst dosage of 0.06?g, and an O/S molar ratio of 4, 100% desulfurization was achieved within 90?min for benzothiophene, dibenzothiophene, and 4,6-dimethyl-dibenzothiophene. The high catalytic activity of HPW(x)/MIL-100(Fe) can be attributed to highly dispersed HPW active sites with a high specific surface area.     

Five-factor response surface optimization of the enzymatic synthesis of citronellyl butyrate by lipase IM77 from Mucor miehei

Response surface methodology (RSM) and a five-level-five-factor central composite rotatable design (CCRD) were used to evaluate the effects of synthetic variables, such as reaction time (3 to 27 h), temperature (25 to 65 °C), enzyme amount (10 to 50%), substrate molar ratio of citronellol to butyric acid (1∶1 to 1∶3), and added water amount (0 to 20%) on molar percent yield of citronellyl butyrate by direct esterification, using lipase IM77 from Mucor miehei. Reaction time and temperature were the most important variables. Substrate molar ratio had no effect on percent molar conversion. Based on contour plots, optimal synthetic conditions were these: reaction time 24 h, temperature 60°C, enzyme amount 20%, substrate molar ratio 1∶1.5, and added water 0%. The predicted molar conversion value was 100%. An actual experimental value of 98% molar conversion was obtained.     

Spectroscopic and Thermal Studies of Mn(II), Fe(III), Cr(III) and Zn(II) Complexes Derived from the Ligand Resulted by the Reaction Between 4-Acetyl Pyridine and Thiosemicarbazide

Transition metal complexes of Mn(II), Fe(III), Cr(III) and Zn(II) metal ions with a general formulas [Mn(L)₂(Cl)₂]·4H₂O (I), [Fe(L)₂(Cl)₂]·Cl·6H₂O (II), [Cr(L)₂(Cl)₂]·Cl·6H₂O (III) and [Zn(L)₂(Cl)₂]·2H₂O (IV) where L = 4-acetylpyridine thiosemicarbazone, have been synthesized and interpreted using CHN elemental analysis, magnetic susceptibility measurements, molar conductance, thermal analysis and spectroscopic techniques; i.e., infrared, electronic UV/vis, ¹H-NMR and mass. The manganese(II), ferric(III), chromium(III) and zinc(II) complexes have octahedral geometry. The molar conductance measurements reveal that the Mn(II) and Zn(II) chelates are non-electrolytes but Fe(III) and Cr(III) have an electrolytic behavior. The IR spectra show that the 4-acetylpyridine thiosemicarbazone free ligand is coordinated to the metal(II) chlorides as a neutral bidentate ligand through both of the lone pair of electrons of the C=N azomethine group and C=S group. X-ray powder diffraction gives an impression that the resulting complexes are amorphous and different from the start materials. The thermogravimetric studies indicate that uncoordinated water molecules are lost in the first and second decomposition steps. The activation thermodynamic parameters E*, ΔH*, ΔS* and ΔG* are estimated from the differential thermogravimetric analysis (DTG) curves using Horowitz–Metzger (HM) and Coats–Redfern (CR) methods. The ligand and its complexes have been screened for antibacterial and antifungal activities against two bacteria; i.e., Escherichia coli (Gram −ve) and Bacillus subtilis (Gram +ve) and two fungi, i.e., tricoderma and penicillium activities).     

Production of 8,11-cis-eicosadienoic acid by a Δ5 and Δ12 desaturase-defective mutant derived from the arachidonic acid-producing fungus Mortierella alpina 1S-4

The Δ5 and Δ12 desaturase (DS)-blocked mutants of an arachidonic acid-producing fungus, Mortierella alpina 1S-4, were obtained. These mutants accumulated 8,11-cis-eicosadienoic acid (20:2n-9). One of the mutants, M226-9, in which Δ5 and Δ12 DS are perfectly blocked, produced 1.68 mg of 20:2n-9 per mL of culture medium (101 mg/g dry mycelia) and no 5,8,11-cis-eicosatrienoic acid (20:3n-9) when grown in a medium containing 4% glucose and 1% yeast extract at 28°C for 2 d and then at 12°C for 12 d. The mycelial lipid comprised 77.4% triacylglycerol (TG) and 9.8% phosphatidylcholine (PC), among others. TG contained 69.0% of the total 20:2n-9, whose percentage in total TG fatty acids was 15.9%. The highest percentage (44.4%) of 20:2n-9 was found in PC. The addition of olive oil to the culture medium enhanced the production of 20:2n-9.     

2,4-二氯-5-磺酰氨基苯甲酸合成工艺研究

2,4-二氯苯甲酸为原料,经氯磺化、氨解、水解酸化三步反应制备了2,4-二氯-5-磺酰氨基苯甲酸(1)。研究了各步反应的影响因素,确定反应的最佳工艺为:n(氯磺酸)∶n(2,4-二氯苯甲酸)=3.5∶1,反应温度为130～140°C,反应时间为3.5h。得产品2,4-二氯-5-磺酰氨基苯甲酸(2)。n(氨水)∶n(2)=4∶1,10～15°C反应3h,盐酸酸化,得到(1),总收率79.3%,纯度98.7%(HPLC),结构经IR与1H NMR证实。     

Spectrophotometric determination of saturated and alpha,beta-unsaturated carbonyl in complex systems at a single wavelength

The simultaneous determination of trace concentrations of saturated and a,β-unsaturated carbonyl compounds in simple or complex systems at a single wavelength is described. From the wavelength of maximum absorbance of the alkaline carbonyl-2,4-dinitrophenylhydrazone determined at a precise time-interval, the total carbonyl, percentage of saturated carbonyl, and μg C = O/Absorbance unit are then subsequently calculated from previously determined trilinear parameters. These parameters are calculated from the relative response of known concentrations of pure (99.6+%) saturated anda,β-unsaturated carbonyl compounds prepared by large-scale high resolution GLC. The method is applicable in simple or complex systems, such as hydrocarbon, aromatic or aliphatic, oxygenated ester, acid, alcohol or ether systems as well as kerosenes and petroleum distillates.     

A bulky phosphite-modified rhodium catalyst for the hydroformylation of unsaturated fatty acid esters

A series of hydroformylation experiments was performed with a high-grade and a technical-grade-derived methyl oleate (MO) and a rhodium catalyst modified by the bulky tris(2-tert-butyl-4-methylphenyl)phosphite. In the hydroformylation of pure methyl oleate, relatively high turnover numbers were obtained (400–500 mol/mol/h) under mild conditions (molar ratio MO/Rh=910, 80–100°C and 20 bar; CO/H₂=1:1, solvent toluene), leading to about 95% conversion in 3 h. Fast isomerization occurs under these conditions to produce the trans oleate. Trans oleate reacts more slowly than cis oleate. At temperatures below 50°C, isomerization does not occur. The use of technical-grade methyl oleate, containing 14% 9,12 diene, methyl linoleate (ML), results in lower reaction rates because dienes form stable π-allylic intermediates, which slowly undergo hydroformylation. More severe conditions were applied to obtain higher rates. The rate varied from 50 to 400 mol/mol/h, depending on conditions (molar ratio MO/Rh=910, T=50–120°C, P = 50–80 bar; CO/H₂=1:1–1:6, solvent, toluene). Several isomers of ML were formed during the reaction. Subsequent hydroformylation of these isomers results in a complicated mixture of products. The product mixture consists predominantly of methyl formylstearate, methyl formyloleate, methyl diformylstearate, and some yet unidentified side products. A comparison of the classic triphenylphosphine-modified catalyst and the bulky phosphite-modified catalyst has shown that the latter is several times more active.