Search

A newly found rabbit stomach peptide, H-Pyr-Val-Asp-Pro-Asn-Ile-Gln-Ala-OH, was synthesized by the solid-phase method. A new polymer support, cross-linked polystyrene-polypropylene composite fiber (IONEX), was employed to facilitate multiple washing processes in chain elongation reactions. β-Cycloheptyl aspartate, Asp (OChp), was employed for the first time in this solid-phase peptide synthesis. In the final step of the synthesis, the peptide was cleaved from the resin, together with other protecting groups employed, by treatment with 1 M trimethylsilyl trifluoromethanesulfonate thioanisole in trifluoroacetic acid. The deprotected peptide was found to be identical with the sample obtained from the natural source.

Per-0-acetylated glycopyranoses were converted by methylthiotrimethylsilane in the presence of boron trifluoride or trimethylsilyl trifluoromethanesulfonate to the corresponding methyl 1,2- trans -1-thioglycopyranosides in a highly stereoselective process.

Polysilylated hydrazines have wide applicability. It is tedious to prepare these compounds by classic means. However, using hexamethyldisilane and 1,2-dimethyl-1,1,2,2-tetraphenyldisilane as counterattack reagents, we synthesized polysilylated hydrazines under alkaline conditions in good to excellent yields. This one-pot method is expedient and more efficient than other procedures. Polysilylated hydrazines were found to react with aldehydes or ketones in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate to give the corresponding hydrazones under anhydrous conditions.

The suitability of the reductive-cleavage method for analysis of the linkage positions in D-fructofuranosyl residues of D-fructans was examined by using sucrose, chicory-root inulin, and Aerobacter levanicum levan as models. Permethylation, and reductive cleavage with triethylsilane in the presence of either boron trifluoride etherate or trimethylsilyl trifluoromethanesulfonate, gave the expected methylated derivatives of 2,5-anhydro-D-mannitol and 2,5-anhydro-D-glucitol. With either catalyst, nonreducing (terminal) D-fructofuranosyl groups and D-fructofuranosyl residues linked at O-1 gave derivatives having the manno configuration as the major product, whereas D-fructofuranosyl residues linked at O-6, and at both O-1 and O-6, gave derivatives having the gluco configuration as the major product. The independent synthesis, and n.m.r.- and mass-spectral characterization, of the methylated 2,5-anhydro-D-mannitol and 2,5-anhydro-D-glucitol derivatives formed from these residues by reductive cleavage are reported.

The fate of 4-linked d -glucopyranosyluronic residues under reductive-cleavage conditions was investigated by using the Klebsiella aerogenes type 54 strain A3 capsular polysaccharide. Treatment of the fully methylated polysaccharide with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane, followed by in situ acetylation, yielded 1,5-anhydro-2,3,4,6-tetra- O -methyl- d -glucitol, 3,4-di- O -acetyl-1,5-anhydro-2,6-di- O -methyl- d -glucitol, and 3- O -acetyl-1,5- anhydro-2,4-di- O -methyl- l -fucitol, as expected, but the expected product of reductive cleavage of the 4-linked d -glucopyranosyluronic residue, namely, methyl 3- O - acetyl-2,6-anhydro-4,5-di- O -methyl- l -gulonate, was not observed. Instead, methyl 2- O -acetyl-3,6-anhydro-4,5-di- O -methyl- l -gulonate ( 6 ) was identified as the sole product of reductive cleavage of the 4-linked d -glucopyranosyluronic residue. That compound 6 arose as a result of rearrangement during reductive cleavage rather than by reductive cleavage of a 5-linked d -glucofuranosyluronic residue, was established by reductive cleavage of the fully methylated polysaccharide following reduction of its ester groups with either lithium aluminum hydride or lithium aluminum deuteride. The products of the latter reductive cleavage were the same as before, except for the absence of 6 and the presence of 4,6-di- O -acetyl-1,5- anhydro-2,3-di- O -methyl- d -glucitol, or its 6,6-dideuterio isomer. Although the reductive-cleavage technique is suitable for the direct analysis of polysaccharides containing 4-linked- d -glucopyranosyluronic residues, it does not establish whether the uronic residue is a 4-linked pyranoside or a 5-linked furanoside. The expected product is, however, derived from the 4-linked d -glucopyranosyluronic residue after sequential methylation, reduction of its ester group and reductive cleavage.

N2-(p-n-Butylphenyl)-2'-deoxyguanosine (BuPdG) and its 5'-triphosphate (BuPdGTP), expected to be inhibitors of eukaryotic DNA polymerase alpha, have been synthesized. BuPdG was synthesized by two methods and characterized by 1H NMR and by chemical relation to guanosine. Direct synthesis involving silylated N2-(p-n-butylphenyl)guanine (BuPG) and 1-chloro-3,5-di-p-toluoyl-2-deoxyribofuranose in the presence of trimethylsilyl trifluoromethanesulfonate gave one alpha and two beta isomers of deoxyribonucleoside as determined by 1H NMR. However, NMR and UV spectra were equivocal in distinguishing between 7 and 9 isomers. The identity of the desired 9-beta-BuPdG was ultimately proved by its independent synthesis from the corresponding ribonucleoside. 1H NMR spectra of the O'-acetylated ribonucleosides of BuPG showed characteristic patterns of O'-acetylated guanosines, and their identity was proved by relating the products of the reaction of isomeric O'-acetylated 2-bromoinosines with p-n-butylaniline and with ammonia: the 2-bromoinosine which gave guanosine also gave the suspected 9-beta-ribonucleoside, BuPGr, and that which gave N7-beta-ribofuranosylguanine also gave the 7-beta isomer of BuPGr. BuPGr was transformed in a multistep procedure to give BuPdG, identical with the major beta isomer obtained by direct deoxynucleoside synthesis. The 5'-monophosphate of BuPdG was obtained by treatment of the nucleoside with phosphoryl chloride in trimethyl phosphate; the monophosphate reacted as the phosphoimidazolyl derivative with pyrophosphate to yield the 5'-triphosphate, BuPdGTP.(ABSTRACT TRUNCATED AT 250 WORDS)

Total synthesis of neomycin B, a pseudo-tetrasaccharide aminoglycoside antibiotic, has been achieved through two key glycosylation reactions. Coupling of 3- O -acetyl-2,6-diazido-4- O -benzyl-2,6-dideoxy- l -idopyranosyl chloride with 5- O -benzoyl-1,2- O -isopropylidene-α- d -ribofuranose under modified Koenigs-Knorr conditions gave 70% of the desired β- l disaccharide ( 3 ) corresponding to neobiosamine in structure. After deisopropylidenation of 3 and acetylation, 1,2-di- O -acetyl-3- O -(3- O -acetyl-2,6-diazido-4- O -benzyl-2,6-dideoxy-β- l -idopyranosyl)-5- O -benzoyl- d -ribofuranose was coupled to HO-5 of 3,2′,6′-tri- N -(benzyloxy-carbonyl)-1- N :6- O -carbonyl-3′,4′-di- O -( o -methoxybenzoyl)neamine, using trimethylsilyl trifluoromethanesulfonate, to give 60% of the pseudo-tetrasaccharide 19 possessing the framework and masked functionality corresponding to neomycin B. Deblocking and reduction of the azido groups then gave neomycin B.

A new procedure for the preparation of the antiviral and antitumor agent 3-deazaguanine (1) and its metabolite 3-deazaguanosine (2) has been developed by reacting methyl 5(4)-(cyanomethyl) imidazole-4(5)-carboxylate (4) and 5-(cyanomethyl)-1- (2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6), respectively, with hydrazine. The 3-deazaguanosine 3',5'-cyclic phosphate (13) was prepared from 5-(cyanomethyl)-1-beta-D-ribofuranosyl-imidazole-4-carboxamide 5'-phosphate. Glycosylation of the trimethylsilyl 4 with 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-ribofuranose in the presence of trimethylsilyl trifluoromethanesulfonate gave the corresponding N-1 and N-3 glycosyl derivatives with alpha-configuration (18 and 20) as the major products, along with minor amounts of the beta-anomers (19 and 21). However, glycosylation of the sodium salt of 4 with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofurano se (17) gave exclusively the beta-anomers (19 and 21) in good yield. Base-catalyzed ring closure of these imidazole nucleosides gave 2'-deoxy-3-deazaguanosine (29), the alpha-anomer 28, and the corresponding N-3 positional isomers 27 and 26. The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1' NMR and UV spectral characteristics and by single-crystal X-ray analysis for 27-29. In a preliminary screening, several of these compounds have demonstrated significant broad-spectrum antiviral activity against certain DNA and RNA viruses in vitro, as well as moderate activity against L1210 and P388 leukemia in cell culture.

The fate of methylated 2-acetamido-2-deoxy-D-glucopyranosyl residues under reductive-cleavage conditions was investigated by using methyl 2-(acetylmethylamino)-2-deoxy-3,4,6-tri-O-methyl-beta-D-glucopyran oside (1), its alpha anomer (8), and fully methylated lacto-N-tetraitol as test compounds. Treatment of 1 with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane gave rise to (1,2-dideoxy-3,4,6-tri-O-methyl-alpha-D-glucopyrano)-2,3-dimethyl- [2,1-d]-2- oxazolinium trifluoromethanesulfonate. Quenching of the reaction by addition of aqueous sodium hydrogencarbonate resulted in hydrolysis of the oxazolinium salt. Compound 8 was fully stable to reductive-cleavage conditions. Thus, participation by the 2-acetamido group is necessary for glycosidic carbon-oxygen bond-cleavage to occur. Treatment of methyl 2-deoxy-2-(ethylmethylamino)-3,4,6-tri-O-methyl-alpha,beta-D-gluco pyranoside under reductive-cleavage conditions resulted in some anomerization, but neither hydrolysis nor reductive cleavage of the glycosidic carbon-oxygen bond was observed, as expected. Reductive cleavage of fully methylated lacto-N-tetraitol gave the products predicted on the basis of these and prior model studies, including 3-O-acetyl-2-(acetylmethylamino)-2-deoxy-4,6-di-O-methyl-D-glucopy ranose derived from the 3-linked 2-acetamido-2-deoxy-beta-D-glucopyranosyl residue.

The methyl glycoside (1) of the α-L-Rhap-(1 → 2)-α-L-Rhap-(1 → 2)-α-L-Rhap-(1 → portion of the group-specific, common antigen polysaccharide of Group B Streptococci has been synthesized. The key compound of the synthesis was methyl 3,4-di-O-benzyl-α-L-rhamnopyranoside (4). Controlled acetolysis of 4 gave 1,2-di-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranose (10), which upon reaction with 4 under catalysis by trimethylsilyl trifluoromethanesulfonate (TMS-Tf) yielded the α-(1 → 2)-linked dirhamnoside. Subsequent rhamnosylation followed by deprotection gave 1. TMS-Tf was also used in rhamnosylation reactions with tetra-O-acetyl-α-L-rhamnopyranose. Acetylation of acceptor alcohols was found to be a major side reaction in the TMS-Tf assisted glycosylations. One-dimensional nuclear Overhauser enhancement differential spectroscopy indicated that, in solution, 1 takes up a bent instead of an extended conformation.

The selective fragmentation reactions of β-trimethylsilylketoximes have been proved to proceed effectively with acid catalysts giving the corresponding nitriles. Cyclic silylketoximes gave unsaturated nitriles. The fragmentation in the Beckmann rearrangement is completely controlled and directed by a trimethylsilyl group to lead the regio- and stereo-specific formation of the double bond. The catalytic fragmentation proceeds with the combination of trimethylsilyl ketoxime acetates and trimethylsilyl trifluoromethanesulfonate giving nitriles in high yields. Excellent stereospecificity of the fragmentation based on the stereochemical outcome was discussed. Simple stereo-controlled synthetic approach to some insect pheromones is also described.

The usefulness of a new deprotecting procedure was demonstrated in the solution syntheses of two porcine spinal cord peptides, designated neuromedin U-8 and neuromedin U-25. Protected neuromedin U-8 (8-residue peptide), prepared by condensation of two fragments, served as a C-terminal amino component for the synthesis of neuromedin U-25 (25-residue peptide). Onto this fragment, five peptide fragments were successively condensed by the azide procedure to construct the entire amino acid sequence of neuromedin U-25, a possible biosynthetic precursor of neuromedin U-8. All protecting groups were cleaved from protected neuromedin U-8 and neuromedin U-25 by 1 M trimethylsilyl trifluoromethanesulfonate-thioanisole in trifluoroacetic acid. The results were compared with those obtained by trifluoromethanesulfonic acid deprotection. In terms of contractile activity in rat uterus, neuromedin U-25 was twice as active as neuromedin U-8.

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) was conveniently used to promote the reaction involving N-alkenyloxazolidin-2-ones and activated nitrones, leading to new 4-substituted 5-azaisoxazolidines in good to excellent yields. This TMSOTf-promoted procedure expanded the scope of reaction of N-vinyloxazolidin-2-ones and nitrones in complementary way to the corresponding classical 1,3-dipolar cycloaddition. Some of these adducts could not be obtained under thermal activation.

Synthese par reaction de l'hexamethyl disiloxane avec l'anhydride de l'acide trifluoromethanesulfonique

The reaction of (E,RS)-3-[(1S)-isoborneol-10-sulf inyl]-1-methoxybuta-1,3-diene1 with benzaldehyde or p-nitrobenzaldehyde, when carried out in dichloromethane in the presence of trimethylsilyl trifluoromethanesulfonate, leads mainly to enantiopure condensed 2-aryl-4-ethylidene-1,5-oxathiocane S-oxides. The reaction path begins with the ionic addition of the enantiopure diene 1 onto the CO group activated by trimethylsilyl cation attack on the carbonyl oxygen. The almost complete diastereoselection observed in the following closure of the eight-membered ring is interpreted as being a consequence of the conformational control on cyclization which leads to the thermodynamically favoured isomer. The crystal structure of the 2,4-dinitrophenylhydrazone of the α,β-unsaturated aldehyde 5, obtained by reacting diene 1 with p-nitrobenzaldeyde, supports the stereochemical results.

Acetonitrile oxide reacts regioselectively with 3-buten-2-one and (E)-4-methoxy-3-buten-2-one to give 5-acetyl-2 and 4-acetyl-3-methylisoxazole 3, respectively. Treatment of ketones 2 and 3 with trimethylsilyl trifluoromethanesulfonate gave the silyl enol ethers 4 and 5, whereas the methyl enol ethers 8 and 9 were obtained via elimination of methanol from the corresponding dimethyl ketals.

The preparation of O-hexofuranosides was accomplished from unprotected 1-thioimidoyl furanosides as donors. The present methodology was first used for the synthesis of octyl galactofuranoside and further extended to D-galactofuranose-containing disaccharides. Within this study, we emphasized the need for additional complexing cations to maintain the furanose ring in its initial size. After experimentation, calcium ion was first used concomitantly with trimethylsilyl trifluoromethanesulfonate, the latter being able to activate the thioimidate and the former being likely to inhibit ring expansion. Moreover, an improvement was performed by using copper(II) trifluoromethanesulfonate which could then meet the requirements as both promoter and complexing agent.

Reaction of silylated 5-substituted uracil derivatives 6 with methyl 2,3,5-tri-O-benzoyl-α-D-arabinofuranoside (3) in the presence of trimethylsilyl trifluoromethanesulfonate afforded a mixture of the corresponding 5-substituted 1-(2,3,5-tri-O-benzoyl-α-D-arabinofuranosyl)uracils 7 and the acyclo 2,3,5-tri-O-benzoyl-1-O-methyl-1-(uracil-1-yl)-D-arabinitols 9 with the methoxy group intact at C-1. Compound 7 was deprotected with methanolic ammonia. Compound 7 was also reacted With Lawesson's reagent to generate the corresponding 4-thio-α-D-arabinofuranoside nucleoside which was deprotected by treatment with methanolic ammonia

A new synthesis of acyclic N,O-acetals 3 and N,S-acetals 5 has been devised by way of a trimethylsilyl trifluoromethanesulfonate promoted formal 2,3-bond fragmentation of 4-heteroatom substituted azetidinones 1 and 4, respectively. This reaction proceeds by nucleophilic attack of a nitrile group of the solvent on the cation intermediate A. However, when there is a second nucleophile such as azidotrimethylsilane in the reaction system, no solvent attack occurs but, rather, the second nucleophile attacks the intermediate to form novel α-azido sulfides 6.

The primary hydroxy group of ethyl 2,3-dideoxy-α-D-erythro-hex-2-enopyranoside (1) was selectively protected and the secondary hydroxy group was deoxygenated via the dithiocarbonate 3 from which ethyl 6-O-(4-methoxybenzoyl)-2,3,4-trideoxy-α-D-trideoxy-α-2-enopyranoside (4) and its regioisomer (5) were produced. These were converted into didehydro nucleosides by glycosylation of silylated heterocyclic bases in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst. The configurations of the anomeric products were assigned by 1H-NMR analysis of the corresponding saturated compounds which were obtained by hydrogenation of the double bond in the carbohydrate moiety. The compounds 9a,b,d, 10a, b, 14a,b,e,f, and 15a,b,e,f did not show any significant activity against HIV or HSV-1. Synthese pyranoider Analoga des anti-HIV-aktiven 3′-Desoxy-2′,3′-didehydrothymidins (D4T) Die prim. OH-Gruppe des Ethyl-2,3-didesoxy-α-D-erythro-hex-2-enopyranosids (1) wurde selektiv zu 2 geschutzt und die sek. OH-Gruppe uber das Dithiocarbonat 3 desoxygeniert. So entstanden 6-O-(4-methoxybenzoyl)-2,3,4-tridesoxy-α-D-glycero-hex-2-enopyranosid (4) und sein Regioisomer 5. Durch Glykosilierung silylierter Nukleobasen mit Trimethylsilyl-trifluormethansulfonat als Katalysator entstanden die entspr. Didehydronukleoside. — Die Konfigurationen der Anomeren wurden durch 1H-NMR-Analyse der zugehorigen gesattigten Verbindungen bestimmt, die durch Hydrieren der Doppelbindung im Kohlenhydratanteil entstanden waren. — Die Verbindungen 9a,b,d, 10a,b, 14a,b,e,f und 15a,b,e,f zeigen keine signifikante Aktivitat gegen HIV oder HSV-1.

Trimethylsilyl trifluoromethanesulfonate catalyzes stereoselective condensation of enol silyl ethers and 2-acetoxytetrahydrofuran or -tetrahydropyran derivatives.

N,N-Bis (trimethylsilyl)amines react with aldehydes or ketones in the presence of trimethylsilyl trifluoromethanesulfonate to give Schiff bases in high yields. In situ utilization of the reaction solution as the Schiff base is also demonstrated.

The complete manuscript of this communication appears in: Angew. Chem. Suppl. 1982, 1707. DOI:10.1002/anie.198217070

The application of acetalization of aldehydes and ketones by alkoxysilanes in the presence of trimethylsilyl trifluoromethanesulfonate catalyst to lactones and di-O-trimethylsilyl-α-diols gave readily the corresponding spiro cyclic ortho esters.

Trimethylsilyl azide (TMSA) was reacted with an oxime ester or a Reissert salt in the presence of trimethylsilyl trifluoromethanesulfonate to give tetrazole derivative. The details of these reactions are examined.

Carbonyl compounds are readily acetalized by alkoxysilanes in the presence of trimethylsilyl trifluoromethanesulfonate catalyst.

Trimethylsilyl fluoride 1 is conveniently prepared by the reaction of trimethylsilyl trifluoromethanesulfonate with potassium fluoride in dimethylformamide containing 18-crown-6 ether.