Showing papers on "Glycal published in 2012"
TL;DR: In vitro recapitulation of key sugar-manipulating enzymes from this pathway is demonstrated and construction of the aminodialdose core of tunicamycin exploits their enol ether motif in a mode of C-C bond formation not previously observed in nature, to create an 11-carbon chain.
Abstract: The tunicamycins are archetypal nucleoside antibiotics targeting bacterial peptidoglycan biosynthesis and eukaryotic protein N-glycosylation. Understanding the biosynthesis of their unusual carbon framework may lead to variants with improved selectivity. Here, we demonstrate in vitro recapitulation of key sugar-manipulating enzymes from this pathway. TunA is found to exhibit unusual regioselectivity in the reduction of a key a,b-unsaturated ketone. The product of this reaction is shown to be the preferred substrate for TunF—an epimerase that converts the glucose derivative to a galactose. In Streptomyces strains in which another gene (tunB) is deleted, the biosynthesis is shown to stall at this exo-glycal product. These investigations confirm the combined TunA/F activity and delineate the ordering of events in the metabolic pathway. This is the first time these surprising exo-glycal intermediates have been seen in biology. They suggest that construction of the aminodialdose core of tunicamycin exploits their enol ether motif in a mode of C–C bond formation not previously observed in nature, to create an 11-carbon chain.
74 citations
TL;DR: A method for the synthesis of a new family of 1-deoxy S-disaccharides has been established via free-radical hydrothiolation of glycals by sugar thiols (thiol-ene coupling) as mentioned in this paper.
34 citations
TL;DR: A temperature-controlled mechanism switch between the Al(OTf)(3)-catalysed direct addition of alcohols or the Ferrier rearrangement reactions in some glycals is presented.
Abstract: A temperature-controlled mechanism switch between the Al(OTf)(3)-catalysed direct addition of alcohols or the Ferrier rearrangement reactions in some glycals is presented. The scope and limitations are investigated as are the influence of the stereochemistry and nature of the protecting groups on the glycal substrate.
28 citations
TL;DR: Derivatives of an antifungal agent that targets the β-(1,3)-D-glucan synthase, papulacandin D, were synthesized and tested for activity, with moderate biological activity observed for the derivatives with a side chain based on palmitic acid and linoleic acid.
Abstract: Derivatives of an antifungal agent that targets the β-(1,3)-D-glucan synthase, papulacandin D, were synthesized and tested for activity. The papulacandin D structure contains a challenging benzannulated spiroketal unit, which is introduced in a palladium-catalyzed cross-coupling reaction of a glycal silanolate and an aryl iodide followed by an oxidative spiroketalization. Four different variants were made, differing in the nature of the acyl side chain with respect to the length, and in the number and stereochemistry of the double bonds. Moderate biological activity was observed for the derivatives with a side chain based on palmitic acid and linoleic acid.
26 citations
TL;DR: Acortatarins A and B have been synthesized via stereoselective spirocyclizations of glycals and acid equilibration and crystallographic analysis indicate that acortatarin B is a contrathermodynamic spiroketal with distinct ring conformations compared to acortatars A.
26 citations
TL;DR: These tc-DNA derivatives increased the stability of duplexes investigated with ΔT(m)/mod of +0.4 to +2.0 °C and the only destabilizing residue was tc(hd)-T, most likely due to self-aggregation of the lipophilic side chains in the single stranded oligonucleotide.
Abstract: Tricyclo-DNA (tc-DNA) is a promising candidate for oligonucleotide-based therapeutic applications exhibiting increased affinity to RNA and increased resistance to nucleases. However, as many other oligonucleotide analogs, tc-DNA does not readily cross cell membranes. We wished to address this issue by preparing a prodrug of tc-DNA containing a metabolically labile group at C(6′) that promotes cellular uptake. Two monomeric nucleoside building blocks bearing an ester function at C(6′) (tcee-T and tchd-T) were synthesized starting from a known C(6′) functionalized bicyclic sugar unit to which the cyclopropane ring was introduced via carbene addition. NIS-mediated nucleosidation of the corresponding glycal with in situ persilylated thymine afforded the β-iodonucleoside exclusively that was dehalogenated via radical reduction. Diversity in the ester function was obtained by hydrolysis and reesterification. The two nucleosides were subsequently incorporated into DNA or tc-DNA by standard phosphoramidite chemis...
23 citations
TL;DR: In this paper, a stereoselective methodology was developed for the construction of cis-fused perhydrofuro[2,3-b]furans via 3-C-branched glycal derivatives, involving Claisen rearrangement of sugar-derived allyl vinyl ethers, followed by a one-pot ozonolysis and acid-mediated acetalization.
17 citations
TL;DR: The coupling efficiency can be further enhanced by in situ benzoylation, as illustrated in an 11-step synthesis of a branched hexasaccharide from glucals in 28% isolated yield and just four chromatographic purifications.
13 citations
TL;DR: This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharide via α-selective glycosylation and hydroamination of glycal in a one-pot manner and allows derivatization by variation of each component.
Abstract: The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each component.
12 citations
TL;DR: In this paper, a method for the preparation of optically active α-hydroxy β-lactams in excellent yields has been proposed, based on the stereochemistry and nature of the glycals.
10 citations
TL;DR: In this article, the reaction of 3-hydroxy free glycals with O- or N-nucleophiles under Mitsunobu reaction conditions proceeded to produce 2,3-unsaturated glycosides in good to high yield and moderate stereoselectivity.
TL;DR: An efficient protocol for the stereoselective synthesis of C-2-methylene-α and -β-C-glycosides by a Claisen rearrangement of 2-vinyloxymethyl glycal derivatives is reported in this article.
Abstract: An efficient protocol for the stereoselective synthesis of C-2-methylene-α- and -β-C-glycosides by a Claisen rearrangement of 2-vinyloxymethyl glycal derivatives is reported A plausible mechanism for the formation of α-selective-C-glycoside was proposed The methodology was further extended to the high diastereoselective synthesis of C-2-methyl-C-glycosides
TL;DR: In this paper, a protected 6-aminopyridine C-nucleoside intermediate was converted into the N-oxide followed by Ac2O-mediated rearrangement and final deprotection to give 6-acetylamino-2-oxo(1H)-pyridin-3-yl deoxyribonucleosides.
TL;DR: Investigation into the selective deprotection of 5′-silyl versus 3′- silyl and subsequent glycosidic bond cleavage are reported herein and both modifications are required for the formation of the furanoid glycal.
Abstract: Thermolytic cleavage of 3′-OH protected thymidine is the most common method of preparing furanoid glycals. We have observed that glycosidic bond cleavage is more facile when the 5′-OH of thymidine was also protected with a silyl group. Addition of trimethylsilyl chloride facilitated cleavage of the glycosidic bond; thus, both modifications are required for the formation of the furanoid glycal. Investigations into the selective deprotection of 5′-silyl versus 3′-silyl and subsequent glycosidic bond cleavage are reported herein.
TL;DR: In this article, D-glucal, D-galactal, and their 6-O-TBDMS derivatives were benzylated in a two-step procedure under microwave conditions.
TL;DR: In this paper, the reaction of persilylated uracil with 3,4-dihydro-2H-pyran in the presence of TMSOTf and PhI(OAc)2 resulted in the formation of a dihydropyranyluracil derivative, although the yield was low.
Abstract: In continuation of our previous study, oxidative coupling reactions of uracil with allylsilane or enol ethers were examined using diacetoxyiodobenzene. The reaction of persilylated uracil with 3,4-dihydro-2H-pyran in the presence of TMSOTf and PhI(OAc)2 resulted in the formation of a dihydropyranyluracil derivative, although the yield was low. In an extension of the oxidative coupling reaction, a novel glycosylation reaction using glycal derivatives as substrates was also developed. The treatment of persilylated uracil and 3,4-dihydro-2H-pyran with (PhSe)2 and PhI(OAc)2 in the presence of a catalytic amount of TMSOTf gave a 2,3-anti-derivative of 1-(3-phenylselanyltetrahydropyran-2-yl)uracil stereoselectively and in good yield.
TL;DR: In this paper, the azidonitration of di-O-acetyl-l-fucal has been shown to be an efficient route to the bacterial aminosugar Nacetyl l-Fucosamine.
TL;DR: 2-Deoxy-2-C-alkyl glycal derivative is a suitable glycosyl donor to prepare 2-deoxy-1,5-anhydro-d-arabino-hex-1-enitol, mediated through haloglycosylation and a subsequent dehalogenation.
Abstract: A method to convert 2-hydroxy glycol ester to the corresponding corresponding 2-deoxy-2-C-alkyl glycol in a facile manner, through key reactions including (i) C-allylation at C-1, (ii) Wittig reaction, and (iii) Cope rearrangement of a 1,5-diene derivative, is reported. The alpha-anomer of the 1,5-diene derivative underwent Cope rearrangement to afford 2-deoxy-2-C-glycal derivative, whereas the beta-anomer was found to be unreactive. Employing this sequence, was transformed to 3,4,6-tri-O-benzyl-2-deoxy-2-C-alkyl-1,5-anhydro-D-arabino-hex-1-enitol. 2-Deoxy-2-C-alkyl glycol derivative is a suitable glycosyl donor to prepare 2-deoxy-2-C-alkyl glycosides, mediated through haloglycosylation and a subsequent dehalogenation. A number of 2-deoxy-2-C-alkyl glycosides, with both glycosyl and nonglycosyl moieties at the reducing end, are thus prepared from the glycol.
TL;DR: Two simple and rapid procedures affording 4β-acylamido- and 4 β-acetoxyneuraminic acid glycals acylated or perfluoroacylated at the 5-amino group are reported.
Patent•
08 Feb 2012
TL;DR: In this paper, the authors present a synthesis method of glycal based on triacetyl-ribose halide in 150 parts of dichloromethane, which is then cooled to a temperature below 10 deg C. The synthesis method provided in the invention has the advantages of simple operation and easily controllable reaction speed.
Abstract: Relating to the technical field of organic synthesis of glycal, the invention specifically relates to a synthesis method of glycal. The method comprises the steps of: dissolving 100 parts of triacetylribose halide in 150 parts of dichloromethane so as to obtain a halogenated sugar solution which is then cooled to a temperature below 10DEG C; mixing 150 parts of dichloromethane, 50 parts of zinc powder, and 100 parts of an ammonium chloride water solution well in a reaction vessel equipped with a condenser; heating the reaction vessel till generating backflow, then stopping heating, adding thehalogenated sugar solution for several times into the reaction vessel at a speed of 100r/min, with the halogenated sugar solution added of 1/20 of the halide solution by mass each time and the backflow generated each time after the adding of the halogenated sugar solution, and adding the halogenated sugar solution again after the end of the backflow, then waiting for the stop of the backflow, thus coming to the end of the reaction. The synthesis method provided in the invention has the advantages of simple operation, easily controllable reaction speed, fixed reaction time, strong repetitive operationality, and convenient product quality control. And the reaction method has high yield and can produce products of high purity.
TL;DR: Reaction of glycal derivatives with alcohols or glycosyl acceptors in the presence of N-bromosuccinimide and diphenyldiselenide resulted in the formation of alkyl 2-deoxy-2-phenylselenyl glycosides or disaccharide derivatives in excellent yield.
Patent•
04 Jan 2012
TL;DR: In this paper, a method for preparing acetylated glycal, disaccharide glycal and benzoylated glycal has been proposed, which has the advantages of simple operation, short process, high yield, fast reaction, low cost, fewer three wastes, energy saving, environment protection, and easy industrialization.
Abstract: The invention belongs to the technical field of organic chemistry, and particularly relates to a method for preparing acetylated glycal, acetylated disaccharide glycal and benzoylated glycal. Acetylated glycosyl bromide or acetylated disaccharide bromide or benzoylated glycosyl bromide is added into a system of PEG and water, and then Zn powder is added to carry out room temperature reaction to respectively generate the acetylated glycal or the acetylated disaccharide glycal or the benzoylated glycal. The invention has the advantages of simple operation, short process, high yield, fast reaction, low cost, fewer three wastes, energy saving, environment protection, easy industrialization and the like.
Patent•
03 Oct 2012
TL;DR: In this article, a postprocessing method for a glycal reaction solution is proposed. But the method is not suitable for large scale production, as it requires time, labor and cost, waste eluent which cannot be processed can not be largely produced.
Abstract: The invention relates to the technical field of glycal, in particular to a postprocessing method for a glycal reaction solution. The glycal reaction solution is washed with acid within one hour until the aqueous phase PH is acidic or neutral, then the glycal reaction solution is washed until the aqueous phase PH is neutral or alkaline, organic phases are separated, and the purified glycal is obtained after drying. According to the postprocessing method for the glycal reaction solution disclosed by the invention, time, labor and cost are saved, waste eluent which can not be processed can not be largely produced, the yield and the purity of the obtained glycal are high, and the method can be used for production on a large scale.
TL;DR: In this paper, the authors investigated the effect of the transition states on the selectivity of a diastereoisomeric d,l-6-deoxy-N-Cbz-imino glycal-derived allyl N-nosyl aziridines.
Patent•
28 Nov 2012
TL;DR: In this paper, the authors provided an addition method of glycal and alcohol compounds, and the addition method comprises the following steps of: a, mixing glycal, alcohol compounds and triphenylphosphine hydrobromide in a first organic solvent for carrying out an addition reaction; b, regulating the pH value of a reaction solution obtained in the step a to be neutral; and c, cleaning a neutral reaction solution by using a second organic solvent to obtain a reaction product.
Abstract: The invention provides an addition method of glycal and alcohol compounds, and the addition method comprises the following steps of: a, mixing glycal, alcohol compounds and triphenylphosphine hydrobromide in a first organic solvent for carrying out an addition reaction; b, regulating the pH value of a reaction solution obtained in the step a to be neutral; and c, cleaning a neutral reaction solution obtained in the step b by using a second organic solvent to obtain a reaction product, wherein the second organic solvent is liquid alkane with a carbon atom number of less than or equal to 10. According to the method provided by the invention, the triphenylphosphine hydrobromide is used as a catalyst, and is relatively smaller in acidity, so that the addition reaction of glycal is higher in reaction efficiency; and glycal can fully react, so that the addition product of glycal is increased. The second organic solvent adopted by the invention can be used for dissolving the catalyst without dissolving the product, so that the catalyst is removed from the reaction solution by adopting the second organic solvent, and the purity of the addition production of glycal is improved.
TL;DR: The reaction of benzyl protected glycal (I) with both aliphatic and aromatic alcohols in the presence of Al(O-Tf)3 proceeds either via addition or via Ferrier rearrangement depending on the reaction temperature as discussed by the authors.
Abstract: The reaction of benzyl protected glycal (I) with both aliphatic and aromatic alcohols in the presence of Al(O-Tf)3 proceeds either via addition or via Ferrier rearrangement depending on the reaction temperature.
TL;DR: In this article, the conformational flexibility of two glycal-type neuraminidase inhibitors has been studied, using several molecular modeling techniques, and an intramolecular hydrogen bond, representing a key structural feature that controls the conformer distribution in solution, has been identified.