Bis Trimethylsilyl Ether Research Articles

One-pot conversion of trimethylsilyl ethers into urethanes using chlorosulfonyl isocyanate: Application to the synthesis of a novel neuromodulator carisbamate

This paper reports a novel synthetic method for the preparation of various urethanes and the application to the synthesis of carisbamate. The reaction of primary (2a, 2e and 2f) or secondary (2g-2i) trimethylsilyl ethers with chlorosulfonyl isocyanate afforded the corresponding urethanes in good yields without affecting the olefin moiety. However, in the case of secondary benzylic trimethylsilyl ether 2j, the corresponding urethane 3j was obtained in low yield. From the difference in reactivity between the primary and secondary benzylic trimethylsilyl ethers, the one-pot synthesis of carisbamate 1 from bis-trimethylsilyl ether 2l was achieved.

Isolation of unsaturated diols after oxidation of conjugated linoleic acid with peroxygenase.

Oat seeds are a rich source of peroxygenase, an iron heme enzyme that participates in oxylipin metabolism in plants. An isomer of CLA, 9(Z),11 (E)-octadecadienoic acid (1), believed to have anticarcinogenic activity, was used as a substrate for peroxygenase in an aqueous medium using t-butyl hydroperoxide as the oxidant. After acidification of the reaction medium, the products were extracted with ethyl ether, converted to their methyl esters, and characterized using HPLC. Major products after reaction for 24 h showed resonances from 1H NMR spectroscopy that were further downfield than the expected epoxides and were thought to be diol hydrolysis products. However, analyses by HPLC with atmospheric pressure chemical ionization MS (APCI-MS) of the putative allylic diols or their bis-trimethylsilyl ether derivatives gave incorrect M.W. The M.W. of the diols could be obtained by APCI-MS after removal of unsaturation by hydrogenation or by EI-MS after conversion of the allylic 1,2-diols to cyclic methyl boronic esters. Data from MS in conjunction with analyses using 1H and 13C NMR showed that the methylated products from 1 were methyl 9,10(threo)-dihydroxy-11 (E)-octadecenoate, methyl 9,10(erythro)-dihydroxy-11(E)-octadecenoate, methyl 9,12(erythro)-dihydroxy-10(E)-octadecenoate, and methyl 9,12(threo)-dihydroxy-10(E)-octadecenoate. Solid-phase extraction without prior acidification and conversion of the products to methyl esters allowed identification of the following epoxides: methyl 9,10(Z)-epoxy-11 (E)-octadecenoate (6M), methyl 9,10(E)-epoxy-11 (E)-octadecenoate, and methyl 11,12(E)-epoxy-9(Z)-octadecenoate. At times of up to at least 6 h, 6M accounted for approximately 90% of the epoxide product. Product analysis after the hydrolysis of isolated epoxide 6M showed that hydrolysis of epoxide 6 could largely account for the diol products obtained from the acidified reaction mixtures.

Investigations into the biosynthetic pathways for classical and ring B-unsaturated oestrogens in equine placental preparations and allantochorionic tissues

In on-going studies of ‘classical’ and ring B-unsaturated oestrogens in equine pregnancy, the products of metabolism of [2,2,4,6,6- 2 H 5 ]-testosterone and [16,16,17- 2 H 3 ]-5,7-androstadiene-3β,17β-diol with equine placental subcellular preparations and allantochorionic villi have been identified. Using mixtures of unlabelled and [ 2 H ]-labelled steroid substrates has allowed the unequivocal identification of metabolites by twin-ion monitoring in gas chromatography–mass spectrometry (GC–MS). Two types of incubation were used: (i) static in vitro and (ii) dynamic in vitro. The latter involved the use of the Oxycell™ cartridge (Integra Bioscience Systems, St Albans, UK) whereby the tissue preparation was continuously supplied with supporting medium plus appropriate cofactors in the presence of uniform oxygenation. [ 2 H 5 ]-Testosterone was converted into [ 2 H 4 ]-oestradiol-17β, [ 2 H 4 ]-oestrone and [ 2 H 3 ]-6-dehydro-oestradiol-17α in both placental and chorionic villi preparations, but to a greater extent in the latter, confirming the importance of the chorionic villi in oestrogen production in the horse. On the basis of GC–MS characteristics ( M + m/ z 477/ 482 (as O-methyl oxime-trimethyl silyl ether), evidence for 19-hydroxylation of testosterone was found in static incubations, while the presence of a 6-hydroxy-oestradiol-17α was recorded in dynamic incubations (twin peaks in the mass spectrum at m/ z 504/ 507, the molecular ion M +). It was not possible to determine the configuration at C-6. The formation of small, but significant, quantities of [ 2 H 4 ]-17β-dihydroequilin was also shown, and a biosynthetic pathway is proposed. In static incubations of placental microsomal fractions, the 17β-dihydro forms of both equilin and equilenin were shown to be major metabolites of [ 2 H 3 ]-5,7-androstadiene-3,17-diol. Using static incubations of chorionic villi, the deuterated substrate was converted into the 17β-dihydro forms of both equilin and equilenin, together with an unidentified metabolite (base peak, m/ z 504/ 506). The isomeric 17-dihydroequilins were also obtained using the dynamic in vitro incubation of equine chorionic villi, together with the 17β-isomer of dihydroequilenin. Confirmation of the identity of 17β-dihydroequilin and 17β-dihydroequilenin was obtained by co-injection of the authentic unlabelled steroids with the phenolic fraction obtained from various incubations. Increases in the peak areas for the non-deuterated steroids (ions at m/ z 414 (17β-dihydroequilin) and 412 (17β-dihydroequilenin) (both as bis-trimethyl silyl ether derivatives) were observed. Biosynthetic pathways for formation of the ring B-unsaturated oestrogens from 5,7-androstadiene-3β,17β-diol are proposed.

Synthesis of Deuterium-Labeled Androst-5-ene-17.BETA.,19-diol and Its 4-Ene Isomer as Internal Standards for the Determination of the 19-Oxygenation of Aromatase Inhibitors Using GC-MS.

[3β, 7, 7, 17α-2H4]Androst-5-ene-17β, 19-diol (6) and [3, 3, 7, 7, -2H4]androst-4-ene-17β, 19-diol (15-d4) were synthesized as internal standards for gas chromatographic-mass spectrometric analysis of the 19-hydroxylation of androst-5-en-17-one (1) and its 4-ene isomer 2, inhibitors of estrogen biosynthesis, using human placental aromatase. Treatment of [7, 7-2H2]3β-tosylate 3 with Zn-NaI-D2O, followed by reduction with NaBD4, gave compound 6 (d4, 79.8 atom%). Compound 15-d4 was synthesized via 3β, 17β-dihydroxy-5-en-7-one 10 as a key intermediate. Deoxygenation of the 5-en-7-one 10 and [7, 7-2H2]17β-hydroxy-4-en-3-one 13-d2, produced from compound 10 in two steps, with AlCl2D2 was used for the deuterium labeling reaction, producing compound 15-d4 (d4, 93.5 atom%). The 19-oxygenation products of aromatase inhibitors 1 and 2 could be analyzed, after NaBH4 reduction, as the corresponding 17β, 19-diol bis-trimethylsilyl ethers using the internal standards 6 and 15-d4.

Investigation of Group Migration in the Fragmentation of Bistrimethylsilyl Ethers of Diols Separated by Rigid Groups

Investigation of Group Migration in the Fragmentation of Bistrimethylsilyl Ethers of Diols Separated by Rigid Groups

A highly sensitive and selective method for the determination of Leukotriene B 4 in human plasma by negative ion chemical ionization/gas chromatography/tandem mass spectrometry

We have developed a highly sensitive and highly selective method for the determination of Leukotriene B 4 (LTB 4) in human plasma using negative ion chemical ionization/gas chromatography/tandem mass spectrometry (NICI/GS/MS/MS) analysis. The developed method was summarized as follows. Deuterated LTB 4 (d 4-LTB 4) was added to human plasma samples as an internal standard, and samples were extracted by a Sep-pak C18 column. Extracted LTB 4 was derivatized into the pentafluorobenzyl ester of bis-trimethylsilyl ether (PFB-TMS-LTB 4) and quantified on the basis of selected reaction monitoring (SRM) at m/z 299 of [M-PFB-2TMSOH] − by NICI/GC/MS/MS analysis, which was the product ion of [M-PFB] −. The detection limit for the quantification of LTB 4 in human plasma was 10 pg ml −1, sufficiently sensitive to determine the concentrations of endogenous LTB 4 in human plasma. The plasma level of LTB 4 measured in healthy male volunteers was 33.85 ± 33.91 pg ml −1 (mean ± S.D. in six volunteers). The technique of MS/MS used in this method offers much greater sensitivity and selectivity than single-stage mass spectrometry. The developed method showed good reproducibility with a simple and rapid extraction procedure, and would be useful for examining the relationship between various disease states and the levels of LTB 4 in biological fluids.

Synthesis and structure of titanium diolate complexes derived from CpTiCl3

The compounds [Cl2CpTi]2(OCH2CH2CH2O) 1, [Cl2CpTi]2(OCH2CMe2CH2O) 2, and [Cl2CpTi]2-(OCHMeCH2CHMeO) 3 were prepared from the reactions of CpTiCl3 and the bis-trimethylsilyl ethers of the diols. Alternatively, these species could be made from the reactions of the diol, imidazole, and CpTiCl3 employing the appropriate stoichiometry. In the presence of excess diol, loss of CpH is observed. In the case of 1,3-propanediol the species [TiCl(HOCH2CH2CH2O)(OCH2CH2CH2O)]24 was isolated. Recrystallization of 4 from THF led to the isolation of [TiCl2(OCH2CH2CH2O)(THF)]25, albeit in very low yield. This chemistry is described and the implications are considered. Compounds 1, 3, 4, and 5 were characterized crystallographically; the parameters are summarized as follows: 1: C2/c (No. 15), a = 12.587(2) Å, b = 9.632(2) Å, c = 15.824(3) Å, β = 107.88(1)°, V = 1811.3(5) Å3, Z = 4; 3: C2/c (No. 15), a = 12.855(2) Å, b = 10.772(2) Å, c = 15.665(2) Å, β = 109.26(1)°, V = 2047.7(5) Å3, Z = 4; 4: P21/n (No. 14), a = 8.911(3) Å, b = 7.821(2) Å, c = 13.986(2) Å, β = 102.56(2)°, V = 951.3(3) Å3, Z = 2; 5: P21/n (No. 14), a = 8.693(3) Å, b = 9.286(2) Å, c = 13.411(2) Å, β = 101.18(2)°, V = 1062.1(4) Å3, Z = 2. Keywords: titanium alkoxides, structure, synthesis.

ChemInform Abstract: PARAMAGNETIC N-PYRROLINOYL DERIVATIVES OF URACIL AND THYMINE

Die Bis-,trimethylsilylether (I) reagieren mit dem 2,2,5,5-Tetramethyl-1-oxyl-pyrrolin-3-carbon- säurechlorid (II) in äquimolaren Mengen bevorzugt am Nl-Atom unter Bildung von (III).

Paramagnetic N-pyrrolinoyl derivatives of uracil and thymine

1. In the reaction of bis-trimethylsilyl ethers of uracil and thymine with 2,2,5,5-tetramethyl-1-oxylpyrroline-3-carboxylic acid, the trimethylsuyl groups are successively substituted by the pyrrolinoyl groups R2CO. 2. In reaction with alcohols, 1,3-bispyrrolinoyluracils preferentially convert into 3-pyrrolinoyluracils. 1-Pyrrolinoyluracils are stronger acylating agents than 3-pyrrolinoyluracils.

Use of a homologous internal standard for the quantification of the major metabolite of prostaglandin F 2α in human urine by multiple ion analysis

A gas chromatographic-mass spectrometric method for quantitative determination of 9α,11α-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid, the major urinary metabolite of prostaglandin F 2α (PGF-M), was developed. The metabolite was analyzed as the dimethyl ester- O-methyloxime- bis-trimethylsilyl ether derivative. The internal standard consisted of a mixture of diethyl ester + monoethyl ester-δ-lactone of PGF-M. Those two species were converted to the 1-methyl-20-ethyl ester derivative during the analytical process. Linear standard curves were developed in the range 0 to 100 ng of injected prostaglandin. The method comprised extraction with Amberlite XAD-2, methylation, chromatography over octadecasilyl-silica, delactonization, remethylation, and chromatography over silicic acid and Lipidex-5000, followed by methoximation, trimethylsilylation, and instrumental analysis. Interassay coefficient of variation, for the analysis of four identical urine specimens, was 7% and intraassay coefficient of variation, when each sample was injected four times, ranged from 3.2 to 6.0%. Specificity, accuracy, and precision of the method were verified by recovery of the metabolite from two different urine pools. The recovery of authentic, underivatized PGF-M added to urine was 99.1 ± 2.4% (mean ± SE, N = 6). The plot of recovered versus added metabolite followed the equation y = 0.936 x + 25.8, with r = 0.9918.

A Convenient Preparation of Cyclopentane-1,2-Dione

Abstract Cyclopentane-1,2-dione 1 has been employed as a synthetic intermediate in the preparation of a variety of organic compounds including propellanes1a, b, iso-coumarones2, and pyrazines3; moreover, the dione 1 shows some promise4 as a potential precursor to the sesquiterpene, modhephene5. Most authors who have reported the synthesis of 1 in recent years have used the method of Acheson, who treated 2-bromocyclopentanone with ferric chloride/water6 and obtained a 40% yield of 1. We required a more efficient preparation of this material and turned to the bromine oxidation7 of the bis-trimethylsilyl ether 2 as a possible alternative. In this regard, diethyl glutarate was cyclized, via the modified acyloin procedure of Bloomfield8, to provide excellent yields of the bis-silyl ether 2; however, treatment of this compound with bromine furnished only small amounts

A sensitive analytical method for pyrrolizidine alkaloids. The mass spectra of retronecine derivatives.

The pyrrolizidine alkaloids in Senecio jacobaea can be hydrolyzed to the common base, retronecine, and derivatized to form the bistrifluoroacetate, bisheptafluorobutyrate, diacetate and bistrimethylsilyl ether. The analysis of the fluorinated compounds by electron capture provides sensitivity for detection of these alkaloids. The bond weakening effect in the ion formed on electron impact, between the allylic carbon and alkyl ester oxygen due to the electron withdrawing fluorinated groups of the ester, changes the driving force for fragmentation from the nitrogen alpha-cleavage reaction to a charge site migration. This yields alkyl-oxygen bond cleavage and formation of a stabilized allylic cation which is the base peak.

Sporidesmins. 8. Ovine ill-thrift in Nova Scotia. 3. The characterisation of chetomin a toxic metabolite of Chaetomium cochliodes and Chaetomium globosum.

Chetomin, one of the antibiotic metabolites of Chaetomium cochliodes and C. globosum has been isolated as an amorphous, glass-like solid. Elemental analysis of chetomin, its diacetate, and its bistrimethylsilyl ether, mass spectroscopy of its tetrathiomethyl derivative, and n.m.r. spectroscopy indicate the molecular formula to be C31H30N6O6S4. The formation of a tetra-S-methyl derivative and a bismonosulphide indicated the presence of two epidithiodioxopiperazine ring systems like those present in chaetocin, a metabolite of C. minutum, a conclusion supported by the close similarity of the c.d. of the two metabolites. The u.v. spectrum of chetomin was the same as that of echinulin. These facts, and an interpretation of the n.m.r. spectra of chetomin and its derivatives, lead us to believe that the molecule contains an indole, an indoline, and two epidithiodioxopiperazine systems. A biogenetically plausible assembly of these structural features is shown [formula (XIII)], but other formulae are possible.

Conversion of Endiol Bis-trimethylsilyl Ethers to Enolizable α-Diketones by Reaction with Bromine

Conversion of Endiol Bis-trimethylsilyl Ethers to Enolizable α-Diketones by Reaction with Bromine