A Practical Route for the Synthesis of Prostaglandin D2 Metabolites

A convenient, efficient route for the total synthesis of 9α, 11β-dihydroxy-13,14-dihydro-15-oxo-PGF₂ 2, a new plasma metabolite of prostaglandin D₂ 1 is described.     

Synthesis of novel crown ethers. Part 1. Coumestan and coumestan analog derivatives of crown ethers

The presented ethylenedioxy compounds5a,5d,6a and6c are examples of novel cyclic ethers, while macrocyclic polyethers represent new crown ether analogues. New coumestan-crowns5a-f, derivatives of 6,7-dihydroxy-3,4-dihydro-2H-dibenzofuran-1-one and 6,7-dihydroxy-3,3-dimethyl-3,4-dihydro-2H-dibenzofuran-1-one6a-e were synthesized from the correspondingo-dihydroxy compounds3a-b,4a-b and ditosylates or dichlorides of di- or triethylene glycol in the presence of K₂CO₃, in DMF/H₂O (15/1) solutions at 65–75 °C for 35 hours. The structure of the macrocyclic ethers obtained were confirmed by¹H-NMR,¹³C-NMR, IR spectra and elemental analyses.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

5,6-二氢-5-氧杂-1,3-二氮杂菲衍生物的合成

以2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(1)为起始原料, 在氢化钠作用下, 通过与羰基α-氢的Claisen缩合反应, 得到3-乙酰基-2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(2), 所得β-二酮与脲、硫脲和脒衍生物分别进行缩合关环, 生成5,6-二氢-5-氧杂-1,3-二氮杂菲衍生物3和4. 在相同的条件下, 吡喃酮1与草酸二乙酯进行缩合反应, 给出3-乙氧乙二酰 基-2,3-二氢-3-氧代-1,3-苯并(c)-α-吡喃(5), 选择3-氨基吡唑、2-氨基咪唑、3-氨基三唑、2-氨基苯并咪唑和3,5-二氨基吡唑-4-偶氮苯与5缩合, 分别环合成5,6-二氢-5-氧杂-1,3-二氮杂菲并和五元含氮杂环衍生物6～10. 所合成的新化合物均经核磁共振光谱、红外光谱及元素分析证明其结构.     

苯并15冠5与钼多酸的组装

以苯并15冠5和钼多酸为原料, 用水热法合成了两个新颖的超分子配合物[Na(B30C10)][Mo₆O₁₉] (1)和[NaL(CH₃CN)][NaL][α-PMo₁₂O₄₀][NaL₂] (L＝B15C5) (2), 并用单晶X射线衍射测定了它们的晶体结构. 配合物1属单斜晶系, 空间群为C2/m, 它包含三个基本单元: Na^＋, B15C5和Mo₆O , 冠醚分子和Na^＋配位, 并通过静电作用力和多酸分子相连. 配合物2属三斜晶系, 空间群为P-1, 它包含一个[α-PMo₁₂O₄₀]^3－离子和三个钠离子配合物. [Na(B15C5)]^＋通过Mo-O-Na-O键和多酸阴离子相连.     

A novel synthesis of carbacyclin analogs via a stereoselective introduction of 15α-hydroxy group

(+/-)-6,9α-Methanoprostaglandin I₃, ($\text{2}$) and (+/-)-5,6-dihydro-6,9α-methano-6β-prostaglandin I₃, ($\text{4a}$) have been synthesized using a new method for the stereoselective introduction of the 15α-hydroxy group via a stereoselective electrophilic addition of phenyl-sulfenyl chloride to the enol ether ($\text{6}$) and ($\text{23}$) respectively.     

Specificity and molecular mechanism of abortificient action of prostaglandins

The paper reports comparison of electrostatic charge and energy distribution on the basis of the CNDO /2 method for six forms of prostaglandins–PGF_2α, PGF_1β, PGE₁, PGE₂, PGB₁, and PGA₁–having diverse physiological action. The isopotential mapping done in three dimension showed that the lower value of electrostatic potential and proximity of the two low energy regions around O₉ and O₁₁ in PGE₂ and PGF_2α is probably responsible for their higher abortificient activity. We also compare here the variation of the long- and short-range interaction between ring–chain and chain–chain portion of different forms and compared them with the variation in their action.     

A convenient TLC schedule for differential separation and quantification of prostaglandins,thromboxanes, and hydroxy fatty acids formed from [1-14C]arachidonic acid in human blood platelets

Eleven TLC solvent systems were evaluated for the separation of prostaglandins F_2α, E₂ and D₂, thromboxane B₂, 12-OH-5,8,10-heptadecatrienoic acid (HHT), 12-OH-5,8,10,14-eicosatetraenoic acid (HETE), and arachidonic acid (AA) from each other. A three-solvent development TLC procedure, which can conveniently be used for routine resolution of mixtures of these metabolites on a single TLC plate, is reported. The method was used for quantification of the metabolites formed from ¹⁴C-labeled AA by washed human platelets.     

A Guide to Thin-Layer Chromatographic Systems for the Separation of Aflatoxin B1, B2, G1 and G2

Abstract

The separation of aflatoxin B₁, B₂, G₁ and G₂ was compared on six commercial silica gel plates in twelve solvent systems. Two of the solvent systems, chloroform: acetone: ammonium hydroxide (90: 10: 0.25) and chloroform: acetone: hexane (85: 15: 20) resolved the four aflatoxins on all the tested plates. The solvent modifier played an important role in the resolution of these compounds. The effect of the hardness of the plate is also discussed.     

Bridging chlorides and hydroxides: syntheses and crystal structures of binuclear and tetranuclear NiII complexes derived from a reduced Schiff-base ligand 2-(2-pyridylmethylamino)ethanesulfonic acid

Two complexes, [Ni(pmt)(Cl)] (1) and [Ni₄(pmt)₄(OH)₄]·8H₂O (2) [Hpmt = 2-(2-pyridylmethylamino)ethanesulfonic acid], were synthesized by different experimental methods in methanol-water mixed solution. Compound 1 crystallizes in triclinic, space group P?1 with unit cell parameters: a = 8.315(2) Å, b = 8.383(2) Å, c = 9.128(2) Å, α = 103.654(2)°, β = 98.125(2)°, γ = 113.154(2)°, V = 548.6(2) ų, Z = 2. A pair of chlorides is μ ₂-bridges linking two Ni^II atoms in forming binuclear complex 1. The coordination environment at Ni^II is distorted square-pyramidal geometry. Compound (2) belongs to monoclinic, space group C2/c, with a = 16.5168(15) Å, b = 18.3718(17) Å, c = 17.5473(16) Å, α = γ = 90°, β = 93.3820(10)°, V = 5315.3(8) ų, Z = 4. Four hydroxides are μ ₃-bridges joining four Ni^II atoms to generate a cubic framework as a tetranuclear complex. The configuration at each Ni^II is distorted octahedral. Both π–π stacking of pyridine rings and intermolecular hydrogen bonds stabilize the solid state structures for 1 and 2.     

Synthesis,structures and magnetic properties of nickel bis (dithiolene) complexes with [Fe(qsal)2]+

Two new compounds containing the possible Fe(III) spin-crossover cation, [Fe(qsal)₂]⁺ (qsalH = N-(8-quinolyl)salicylaldimine), and nickel bis(dithiolene) anions have been synthesized. Both are 1 : 1 salts [Fe(qsal)₂][Ni(dddt)₂] · CH₃CN · CH₃OH (1) and [Fe(qsal)₂][Ni(pddt)₂] (2) (dddt = 5,6-dihydro-1,4-dithiin-2,3-dithiolate; pddt = 6,7-dihydro-5H-1,4-dithiepin-2,3-dithiolate). They have been characterized by X-ray crystal structure determination, elemental analysis, UV-Vis spectra and magnetic susceptibility measurements. The UV–Vis spectra are dominated by [Ni(L)₂]^? (1, L = dddt; 2, L = pddt). Magnetic studies show antiferromagnetic interaction in 1 from intermolecular S···S contacts and π–π stacking interactions, while the antiferromagnetic interaction in 2 is very weak.     

Two new alkaloids from Melodinus hemsleyanus Diels

Two new monoterpenoid indole alkaloids, named 14,15-dihydro-14β,15β-epoxy-10-hydroxyscandine (1) and 15α-hydroxy-meloscandonine (2), together with 12 known compounds, were isolated from the aerial parts of Melodinus hemsleyanus Diels. The structures of 1 and 2 were elucidated on the bases of 1D and 2D NMR spectra and MS. Two new compounds were evaluated for their PTP1B and Drak2 inhibitory effects, and inactivity.     

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis

Chemical investigation on CH₂Cl₂ extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (2) along with ten known related steroid analogs (3–12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC₅₀: 3.0 and 5.6?μM), PC9 (2.0 and 15.6?μM), and MCF-7 (9.4 and 11.8?μM) cell lines, respectively.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Cytotoxic constituents of Lasiosphaera fenzlii on different cell lines and the synergistic effects with paclitaxel

The fruit body of Lasiosphaera fenzlii was found to show cytotoxicity on cancer cells during a preliminary screening. Repeated column chromatography of the fungal methanol extract resulted in the isolation of six compounds identified as 5α,8α-epidioxy-ergosta-6,22-dien-3β-ol (1), 5α,8α-epidioxy-ergosta-6,9(11),22-trien-3β-ol (2), 5α-ergosta-7,22-dien-3β-ol (3), 5α-ergosta-7,22-dien-3-one (4), ergosta-7,22-dien-3β,5α,6β-triol (5) and 6-dihydroxy-2,3-dihydro-1H-isoindol-1-one (6). The two peroxide compounds, 1 and 2, showed cytotoxic activity and compound 1 was selectively cytotoxic to cancer cells. Furthermore, compound 1 synergised the cytotoxicity of paclitaxel on Hela cells by increasing intracellular accumulation of paclitaxel in cancer cells but not in normal cells.     

New Synthesis of Simvastatin

A noninfringing synthesis of simvastatin 1, starting from lovastatin 2, is presented. This synthesis features the protection of the free hydroxyl group of the lovastatin with 3,4-dihydro-2H-pyran (DHP) and opening of the lactone ring with n-BuNH₂ to afford amide 4 as a key intermediate.     

Two new 14, 15-secopregnane-type steroidal glycosides from the roots of Cynanchum limprichtii

Two new steroidal glycosides 1 and 2, along with three known ones (3–5), were isolated from the 95% ethanol extract of the roots of Cynanchum limprichtii Schltr. The structure of the new compounds was elucidated as 3-O-α-L-diginopyranosyl-(1→4)-β-D-digitoxopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-thevetopyranosyl-14, 16:15, 20:18, 20-triepoxy-14, 15-secopregn-4, 6, 8 (14)-triene (1) and 3-O-α-L-cymaropyranosyl-(1→4)-β-D-digitoxopyranosyl- (1→4)-β-D-3-demethyl-2-deoxythevetopyranosyl-14, 16: 15, 20: 8, 20-triepoxy-14, 15-secopregn-5, 8 (14)-diene (2) on the basis of spectroscopic analysis together with acidic hydrolysis. All compounds showed cytotoxic activity against the human cancer cell line HL60, with IC₅₀ values of 55.36, 65.41, 17.88, 17.68 and 33.5 μM, respectively. While, only compound 3 showed cytotoxicity against the Caco-2 cell line, with an IC₅₀ value of 67.47 μM.     

The Acetoxyfulvene Synthesis of Prostaglandins: A New,Versatile Synthesis of dl-PGF1δ, dl-PGF2α, dl-PGE1 and dl-PGE2 from a Common Intermediate

Abstract

In the Corey¹ synthesis of prostaglandins and in our recently published modifications^2,3 a synthon containing carbon atoms 14 to 20^θ is first added to a bicyclic intermediate (C-6 to C-13) and completion of the prostaglandin skeleton by addition of a second synthon containing carbon atoms 1 to 5 forms a subsequent step. In a modification^4,5 of the Corey synthesis¹ PGF_1α and PGE₁ were made by reversing the order in which these two synthons were added to the cyclopentane ring (C-6 to C-13). The major limitation of this modified route^4,5 is that it is restricted to the preparation of prostaglandins of the 1-series,^? because hydrogenolysis of the benzyl group of the intermediate ester (1) reduces the C-5, C-6 double bond to form the saturated alcohol (2), which cannot be converted into prostaglandins of the 2-series^?.     

Über Reaktionen cyclischer Oxalylverbindungen, 7. Mitt.

Zusammenfassung Benzamidoxim reagiert mit Oxalylchlorid zum Oxadiazino-oxadiazin-Derivat3. Benzamidoxim-äther und Oxalylchlorid cyclisieren sich je nach Reaktionsdauer in siedendem Xylol über das entsprechende Imidazolium-Salz4 entweder zum 3-Phenyl-4,5-dihydro-1,2,4-oxadiazol-5-on (7) oder, wie im Falle des Äthyl-äthers, zur Verbindung5 (C₁₁H₁₂N₂O₂).

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Reactions of cyclic oxalyl compounds, VII: Syntheses of heterocycles, CLXIII

Benzamide oxime reacts with oxalyl chloride (molar rate 21) to give the oxadiazino-oxadiazine derivative3. Benzamide oxime O-ethers and oxalyl chloride cyclize in boiling xylene yielding 3-phenyl-4.5-dihydro-1.2.4-oxadiazol-5-one (7) or5, depending on the reaction time. The imidazolium salt4 is postulated as the common intermediate.

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Herrn Prof. Dr.H. Kämmerer, Universität Mainz, mit freundschaftlichen Grüßen zum 60. Geburtstag gewidmet.     

Tagetnoic acid,a new lipoxygenase inhibitor peroxy fatty acid from Tagetes minuta growing in Saudi Arabia

Abstract

A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were separated from the n-hexane fraction of the aerial parts of Tagetes minuta L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds 3–5 displayed potent lipoxygenase inhibitory potential with IC₅₀s 2.26, 1.83, and 1.17?μM, respectively compared to indomethacin (IC₅₀ 0.89?μM). Moreover, molecular docking study revealed that the potent activity of 5 is due to H-bonding and hydrophobic interaction. The results of this study suggested that Tagetes minuta dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.