O-trimethylsilyl Ethers Research Articles

2,4-Diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfides, their structure and S-silyl dithiophosphonic derivatives

GRAPHICAL ABSTRACT

Synthetic study of 3-fluorinated sialic acid derivatives

Sialic acid derivatives, analogs, and their conjugates are expected to be pharmaceutical candidates such as anti-influenza drugs and also useful probes for investigating the biological role of glycoconjugates. Derivatives of 3-fluorinated sialic acid (3-F-Sia) have been found to be excellent probes in investigating functions and mechanisms of a series of proteins. Here, we describe the syntheses of 3-F-Sia derivatives, which are useful in making biologically important conjugate probes. A practical method for the construction of 3-fluorinated sialosides based on the stereoselective formation of the corresponding anomeric O-trimethylsilyl ether and their nucleophilic attack by an alkyl halide, an allyl halide in particular, was developed. In addition, details of the synthesis of cytidine monophosphate (CMP)-3-F-Sia bearing a fluorescent tag, which has been proven to show dual functions as a substrate of CMP-sialic acid transporter (CST) and an inhibitor of sialyltransferase (STase), are described.

Optimization of an isotope dilution gas chromatography/mass spectrometry method for the detection of endogenous estrogen metabolites in urine samples

A gas chromatography/mass spectrometry (GC/MS) method for the simultaneous quantitation of ten estrogen metabolites in human urine was optimized. The method consists of initial enzymatic hydrolysis of the estrogen conjugates using beta-glucuronidase followed by solid-phase extraction (SPE) on Sep-pak C18 columns and further sample purification by ion-exchange chromatography on QAE-Sephadex cartridges in the acetate form. QAE-Sephadex cartridges in the borate form were used to separate estrogens into two fractions: one fraction containing estrogens lacking vicinal cis-hydroxyls (Fr 1) and another containing estrogens possessing vicinal cis-hydroxyls (catecholestrogens; Fr 2). Finally, following O-trimethylsilyl ether derivatization, the estrogens were analyzed by GC/MS in the selected ion monitoring mode. Estrogens were quantitated using deuterated internal standards, which were added to the samples at the initiation of the work-up procedures. After addition to estrogen-low male human samples the standards showed good chromatographic linear response and reproducibility. A reduction in the number of steps and improvements in the robustness of the work-up procedures were achieved. The modified method described is less complex, amenable to use with commercially available SPE columns and fulfils all the reliability criteria, resulting in highly specific and accurate results.

Asymmetric Synthesis of 2-(2-Pyridyl)aziridines from 2-Pyridineimines Bearing Stereogenic N-Alkyl Substituents and Regioselective Opening of the Aziridine Ring

The addition of chloromethyllithium to the imine derived from 2-pyridinecarboxaldehyde and (S)-valinol, protected as its O-trimethylsilyl ether, gave the 1,2-disubstituted aziridine with good yield and diastereoselectivity. The analogous reaction performed on the imine derived from (S)-valine methyl ester gave the product containing the aziridine ring and the alpha-chloro ketone group coming from the attack of chloromethyllithium to the ester function. Other stereogenic alkyl substituents at nitrogen gave less satisfactory results. Moreover, the aziridination protocol did not work on other aromatic imines which were not capable of bidentate chelation, e.g., 3- and 4-pyridineimine and benzaldimine. Preliminary studies showed the possibility to carry out regio- and stereospecific opening reactions of 2-(2-pyridyl)aziridines by attack of internally generated or external nucleophiles.

α-(Trifluoromethyl)amine Derivatives via Nucleophilic Trifluoromethylation of Nitrones

(Trifluoromethyl)trimethylsilane (TMSCF(3)) reacts with nitrones to afford alpha-(trifluoromethyl)hydroxylamines protected as O-trimethylsilyl ethers. Potassium t-butoxide initiates the nucleophilic trifluoromethylation. The reaction works best with alpha,N-diaryl nitrones, and the conditions are compatible with a range of substituents on the aryl groups. Acidic deprotection of the nitrone/TMSCF(3) adducts generates alpha-(trifluoromethyl)hydroxylamines. Catalytic hydrogenation of the adducts produces alpha-(trifluoromethyl)amines. Nitrone/TMSCF(3) adducts with strong electron-withdrawing groups on the alpha-aryl ring or heterocyclic alpha-aryl groups undergo an elimination/addition sequence to generate alpha,alpha-bis(trifluoromethyl)amines. Nitrones with alkyl groups bound directly to the 1,3-dipolar moiety fail to react with TMSCF(3), but trifluoromethylation of beta,gamma-unsaturated nitrones followed by reduction of the double bond can circumvent this limitation.

Analysis of olive and hazelnut oil mixtures by high-performance liquid chromatography–atmospheric pressure chemical ionisation mass spectrometry of triacylglycerols and gas–liquid chromatography of non-saponifiable compounds (tocopherols and sterols)

We analysed the triacylglycerol, tocopherol and sterol composition of hazelnut oil, olive oil and their mixtures (90% olive oil with 10% hazelnut oil, 70% olive with 30% hazelnut oil and 50% olive oil with 50% hazelnut oil). The main triacylglycerols were 1,2,3-trioleylglycerol, 2,3-dioleyl-1-palmitoylglycerol, 2,3-dioleyl-1-linoleylglycerol and 2,3-dioleyl-1-stearoylglycerol. Non-saponfiable compounds (tocopherols and sterols) were derivatised as O-trimethylsilyl ethers. α-Tocopherol was the main vitamin E isomer in all samples; however, small amounts of β-tocopherol and γ-tocopherol were also found. β-Sitosterol and Δ 5-avenasterol were the principal sterols in all samples; campesterol and stigmasterol were minor sterol compounds in all samples. Obtusifoliol, which was a major sterol in olive oil and oil mixtures, was not found in hazelnut oil. The discriminant analysis showed that hazelnut oil, olive oil and oil mixtures were clearly separated according to their triacylglycerol composition.

Methyl exchange on silicon during the addition of methylmagnesium iodide to a cyanohydrin O-silyl ether

Reaction of [13C]methylmagnesium iodide (99 atom% 13C) with cyanohydrin O-trimethylsilyl ether 1, followed by acidic hydrolysis, led to the formation of a methyl ketone derivative 2a that was only partially labelled (60 ± 5 atom% 13C); this loss of labelling occurred through a methyl exchange reaction on silicon as shown by the presence on intermediate 2b of [13C]methyl groups on silicon (30 atom% 13C).

Di- d-fructose dianhydrides and related oligomers from thermal treatments of inulin and sucrose

Thermal treatment of anhydrous, acidified sucrose or inulin yields caramels containing monosaccharides and oligomers, predominantly dianhydrides and higher oligomers derived by the addition of glycosyl residues to dianhydrides. Fourteen dianhydrides, most of which comprise two fructose moieties, have been identified by mass spectroscopy of the per- O-trimethylsilyl ethers. Thirteen of these dianhydrides have been isolated and characterized; five of the dianhydrides are novel compounds and one of these is a glucose-fructose dianhydride. The dianhydrides and related oligomers are thought to have a prebiotic effect by stimulating the proliferation of bifidobacteria in the large intestine.

Stereoselective synthesis of (1R,2S)-2-amino-1,3-diols from (R)-cyanohydrins

Vinyl substituted (1R,2S)-amino alcohols 5 were obtained by addition of vinyl magnesium bromide to the corresponding cyanohydrin O-trimethylsilyl ethers (R)-2. The O- and N-protected vinyl amino alcohols 6 were ozonized at −78°C in methanol yielding (1R,2S)-2-amino-1,3-diols7 in high enantiomeric and diastereomeric excesses. For purification, compounds 7 in some cases were acetylated to give the derivatives (1R,2S)-8. Racemic 6a was converted by oxidative ozonolysis at −78°C in methanolic NaOH solution to the corresponding methyl N-acetyl-β-hydroxy propanoate 9a. The configuration of (1R,2S)-8a was confirmed by x-ray crystallographic analysis.

Convenient Synthesis of 4-Alkyl, Alkenyl, and Alkynyl Substituted N-(Phenylsulfonyl)indoles.

The indolone 1 reacted with organomagnesium or lithium reagents to give the carbinols 6 and 10, which, upon treatment under appropriate acidic conditions or neutral thermal conditions, gave the 1-phenylsulfonylindoles 8 and 11 bearing various kinds of alkyl, alkenyl, and alkynyl substituents at the 4-position. The indolone 1 was also converted to the 4-cyanoindole 14 via the cyanohydrin O-trimethylsilyl ether 13.

Fragmentation pathways of O-trimethylsilyl ethers of dihydroxy long-chain bases analysed by linked-scan mass spectrometry

The fragmentation pathways of O-trimethylsilyl (TMS) ethers of long-chain bases were studied by the linked-scan technique and exact mass measurements of the characteristic ion of O-trimethylsilyl long-chain bases detected by gas chromatography combined with electron-impact mass spectrometry. The results indicate that there are three pathways: the M + − 15 (CH 3) − 90 (TMSOH) − 74 [OSi(CH 3) 2] series, the M + − 103 (CH 2OTMS) − 90 (TMSOH) series and the M + − 132 (CHNH 2CH 2OTMS) series.

Pigments of Fungi. XV. An Efficient, Unambiguous Route to Unsymmetrically Substituted Dibenzyl Acyloins and Their Use in the Synthesis of Fungus Pigments of the Pulvinone and Grevillin Types

Dibenzyl acyloins including those bearing unsymmetrically disposed aryl residues are assembled in high yield by reaction between the O-trimethylsilyl ethers of arylacetaldehyde cyanohydrins and benzyl Grignard reagents. These acyloins are deprotonated with lithium diisopropylamide to afford alcoholate-enolate dianions which can be made to react with carbonyldiimidazole and with oxalyldiimidazole, respectively, to ultimately afford fungus pigments of the pulvinone and grevillin types.

Gas chromatographic behaviour of carbohydrate trimethylsilyl ethers : II. Aldohexoses

The tautomeric forms of the eight aldohexoses were separated as their O-trimethylsilyl ethers on several packed and capillary columns. Their chromatographic behaviour was similar to that previously found for aldopentoses, but different from that of other ethers. A mathematical approach developed for aldopentoses was applied to aldohexose retention indices on several stationary phases, in an attempt to relate these values to their structural characteristics.

Unusual o-alkylation with iodomethyltrimethylsilane

Iodomethyltrimethylsilane alkylates alkoxide ions giving rise to O-methyl and O-trimethylsilyl ethers which are formed by cleavage of the silicon–carbon bond.

Gas chromatographic behaviour of carbohydrate trimethylsilyl ethers: I. Aldopentoses

The four components of each aldopentose were separated as O-trimethylsilyl ethers on several packed and capillary columns. In order to establish which characteristics affect the retention and to achieve a better understanding of the chromatographic behaviour of these compounds, a mathematical approach was applied which tries to relate structural characteristics with retention indices on several stationary phases.

Capillary gas chromatography of hydroxylated bile acid stereoisomers of the allo and normal series.

Relative retention times and methylene unit (MU) values were determined for 56 bile acids of the allo (5 alpha, A/B-trans) and normal (5 beta, A/B-cis) series, which differ from one another in the number, position and configuration of the hydroxyl groups at positions C-3, C-6, C-7 and/or C-12. The bile acids were derivatized to their methyl ester O-trimethylsilyl ethers (Me-TMS) and methyl ester O-dimethylethylsilyl ethers (Me-DMES), and chromatographed on fused-silica capillary columns, chemically bonded with non-selective OV-1 and selective PEG-20M liquid phases. Of the four possible combinations of derivatives and columns examined, Me-DMES on OV-1 and Me-TMS on PEG-20M were most suitable. The differences in the MU values between the 5 alpha- and 5 beta-series, and between the Me-DMES and Me-TMS ether derivatives, are also summarized. These retention data would be helpful in the identification of closely related bile acid stereoisomers or for estimation of their structures. photolysis.

Determination of the structure of partially methylated sugars as O-trimethylsilyl ethers by gas chromatography-mass spectrometry.

The separation and structural determination of ten partially methylated methyl glucosides by gas chromatography and gas chromatography-mass spectrometry are described. These glucosides were four possible structures for methyl tri-O-methylglucosides and six for methyl di-O-methylglucosides. The positions of free hydroxyl groups in four isomers of methyl tri-O-methylglucosides could be fairly distinguished from each other by their mass spectra. Mass spectra of methyl di-O-methylglucosides were similar to each other, though their spectra were different from those of fully methylated or methyl tri-O-methylglucosides. After introduction of a trimethylsilyl group to the free hydroxyl group, mass spectra of methyl di-O-methylglucosides showed a characteristic pattern for the position of the trimethylsilylated hydroxyl group, and O-trimethylsilyl ethers of methyl tri-O-methylglucosides also showed distinguishable mass spectra. The structures of fragment ions of partially methylated methyl glucosides were confirmed by high resolution mass spectrometry.

Gas-liquid chromatographic separation of ceramides as di- O-trimethylsilyl ether derivatives

Gas-liquid chromatographic separation of ceramides as di- O-trimethylsilyl ether derivatives

Formation of partially trimethylsilylated derivatives of carbohydrates. The trimethylsilyl tris- o-trimethylsilyl- d-glucopyranosides and tetrakis- o-trimethylsilyl- d-glucose

When mixtures of the α and β anomers of benzyl d-glucopyranoside, and of 2-, 3-, 4-, and 6- O-benzyl- d-glucose were treated with hexamethyldisilazane, the tetrakis- O-trimethylsilyl derivatives of the benzyl glycosides and the tris- O-trimethylsilyl ethers of the trimethylsilyl glycosides were obtained (anomeric mixtures). On hydrogenolysis of the trimethylsilyl 2-, 3-, 4-, and 6- O-benzyl-tris- O-trimethylsilyl glycosides, the α- and β-anomers of the trimethylsilyl tris- O-trimethylsilyl- d-glucosides having the following substitution patterns were obtained, respectively: 3,4,6; 2,4,6; 2,3,6; and 2,3,4. The anomers were separated by gas-liquid chromatography. Hydrogenolysis of benzyl tetrakis- O-trimethylsilyl-α,β- d-glucopyranoside gave mainly a mixture of trimethylsilyl tetrakis- O-trimethylsilyl-α- and β- d-glucosides. Direct trimethylsilylation of α- and β- d-glucose with limiting amounts of trimethylsilyl donor [hexamethyldisilazane or N-(trimethylsilyl)acetamide] yielded complex mixtures of partially trimethylsilylated derivatives. The composition of such mixtures has been determined by g.l.c. The major components were the trimethylsilyl tetrakis- O-trimethylsilyl and the 2,3,6- and 2,4,6-tris- O-trimethylsilyl- d-glucosides.

The pyrolysis of some hexoses and derived di-, tri-, and poly-saccharides

The vacuum pyrolysis of glucose, galactose, mannose, fructose, and certain derived di-, tri-, and poly-saccharides gives, as major products, 1,6-anhydrohexo-pyranoses and -furanoses and 5-hydroxymethylfurfuraldehyde. These, together with some minor products, have been estimated as the O-trimethylsilyl ethers by gas chromatography. The pyrolytic reactions, which in many respects resemble acid-catalysed reactions in aqueous solution, are discussed, particularly in relation to the influence of thermally induced conformational changes. Glucose is shown to undergo mutarotation and condensation–polymerisation in the molten state; the pyrolysis products are those of the resulting polymer.