Showing papers on "Glycal published in 1999"
TL;DR: This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
Abstract: The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
140 citations
TL;DR: Differentially protected Glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful glycosyl donors and an orthogonal coupling strategy using glycosol phosphate donors and thioethyl glycoside acceptors allows for the rapid synthesis of a trisaccharide.
120 citations
TL;DR: CMP-3-fluoroneuraminic acid, a useful mechanistic probe for sialyltransferases, has been efficiently synthesized using recent fluorination and phosphorylation techniques from a sialic acid glycal.
52 citations
TL;DR: In this article, a reaction mechanism based on heteroatom abstraction is proposed to give an intermediate glycosyl radical, which reacts with a second equivalent of Ti(III) to yield a glycosyltitanium(IV) species.
Abstract: Glycosyl chlorides and bromides can be rapidly converted to glycals in high yield by reaction with (Cp2Ti[III]Cl)2. This reagent tolerates a wide range of common carbohydrate protecting groups, including silyl ethers, acetals, and esters; the methodology provides a general route for the preparation of glycals substituted with both acid- and base-labile functionality. A reaction mechanism is proposed that is based on heteroatom abstraction to give an intermediate glycosyl radical. This radical reacts with a second equivalent of Ti(III) to yield a glycosyltitanium(IV) species. β-Heteroatom elimination from the glycosyltitanium(IV) complex gives the glycal.
49 citations
TL;DR: Two novel routes to C-linked glycosyl amino acids are described; the first involves elaboration of an exo-glycal and subsequent Ramberg–Backlund rearrangement of a sulfone intermediate to give, after functional group manipulation, a protected C-glycosyl serine.
43 citations
TL;DR: The DCC mediated coupling reaction of 3,4,6-tri-O -benzyl-1,2-dideoxy-d -arabino-hex-1-enitol gave esters 7a-d in good yield as mentioned in this paper.
39 citations
TL;DR: The synthesis of the Fmoc-protected C-glycosyl tyrosines 1 and 2, together with two other related C-symmetric cyclic oligopeptide 4, has been achieved.
Abstract: The synthesis of the Fmoc-protected C-glycosyl tyrosines 1 and 2, together with two other related C-glycosyl tyrosines, has been achieved. Key reactions involved (i) the reaction of a glycal with an organozinc reagent (carrying an aryl iodide function) in the presence of a Lewis acid to establish the C-glycosyl linkage and (ii) subsequent cross coupling of the aryl iodide to an alanyl zinc reagent (in the presence of a Pd(0) catalyst) to complete the construction of the α-amino acid moiety. Using solid-phase peptide synthesis methods, two units of the mannosyl derivative 1 (shown as l-Tyr[C-Ac4-α-d-Man]) have been incorporated (with four units of glycine) into the linear hexapeptide 3 which was then converted to the C2-symmetric cyclic oligopeptide 4.
30 citations
TL;DR: In this article, the bromide with Cp2TiCl2 and Mn in THF was used to eliminate the acetylated glycosyl bromides to the corresponding glycal.
18 citations
Patent•
06 Oct 1999TL;DR: One aspect of the present invention relates to differentially protected glycosyl phosphates as mentioned in this paper and another aspect relates to the preparation of glycoly phosphates from glycal precursors.
Abstract: One aspect of the present invention relates to differentially protected glycosyl phosphates. Another aspect of the present invention relates to the preparation of glycosyl phosphates from glycal precursors. In another aspect of the present invention, glycosyl phosphates are used as glycosyl donors in glycosylation reactions.
17 citations
TL;DR: In this paper, the 1,2-unsaturated furanoid glycal undergoes coupling reaction to produce 2,3-unaturated products (1a,b) as pure stereoisomers.
14 citations
TL;DR: Hydroxyfluorination of glycal was successfully conducted using SiF4-PhI(OAc)2-H2O to give fluoroglucose in 73% yield and subsequent debromination with n-Bu3SnH gave 2-deoxy sugars in good yields.
TL;DR: Under basic conditions, phenyl 1, 2-dithio-α-d-mannopyranoside forms a glycal-1,2-episulfide, which undergoes controlled oligomerization to afford a family of thio-oligo-β-D-mannOPyranosides, which might have application as mimics of natural structures such as viral high-mannose glycoproteins or ManLAM.
TL;DR: The cis amino alcohol functionality in vancosamine was introduced by the electrophilic cyclization of the isourea, followed by hydrolysis of the resulting oxazoline, which led to the synthesis of methyl α- l -vancosaminide.
TL;DR: The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized in this paper, and it has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols.
Abstract: The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
TL;DR: In this article, the synthesis of Fmoc-protected C-glycosyl tyrosines 1 and 2, together with two other related C-Glycosyl Tyrosines, has been achieved.
Abstract: The synthesis of the Fmoc-protected C-glycosyl tyrosines 1 and 2, together with two other related C-glycosyl tyrosines, has been achieved. Key reactions involved (i) the reaction of a glycal with an organozinc reagent (carrying an aryl iodide function) in the presence of a Lewis acid to establish the C-glycosyl linkage and (ii) subsequent cross coupling of the aryl iodide to an alanyl zinc reagent (in the presence of a Pd(0) catalyst) to complete the construction of the α-amino acid moiety. Using solid-phase peptide synthesis methods, two units of the mannosyl derivative 1 (shown as l-Tyr[C-Ac4-α-d-Man]) have been incorporated (with four units of glycine) into the linear hexapeptide 3 which was then converted to the C2-symmetric cyclic oligopeptide 4.
TL;DR: In this paper, a qualitative correlation of reactivity with the HOMO−LUMO gap between the glycal (HOMO) and the heterodienic species (HUMO) is observed.
Abstract: Diacyl thione species 1 has been generated and reacted in situ with both pyranoid and furanoid glycals to form novel [4 + 2] cycloadducts. Factors such as protecting groups and configuration of substituents in the glycals along with medium effects were varied to discover influences on face selectivity and reactivity. A qualitative correlation of reactivity with the HOMO−LUMO gap between the glycal (HOMO) and the heterodienic species (LUMO) is observed. In one example, the isolation of byproducts suggests that the cycloaddition may in fact be stepwise.
TL;DR: The CDE-trisaccharide of chromomycin A3 was cleaved with samarium diiodide and converted to a protected glycal for coupling to an aglycone.
TL;DR: In this paper, the synthesis of C-glycopyranosyl compounds has been studied in the context of cell recognition and differentiation processes, and the first approach has been to link a C-N synthon (HCN or CH 3 NO 2 ) to the anomeric carbon of a natural carbohydrate.
Abstract: C-glycopyranosyl compounds exhibit antimicrobial, antifungal, and antitumor activities, most probably based on enzyme inhibition or interference with cell surface recognition phenomena. Recent developments in glycobiology have shown the importance of the glycoside component of glycoproteins for cell recognition and differentiation processes. C-glycosidic analogues of that component would be metabolically stable, and thus offer enhanced therapeutic value. Synthesis of a configurational variety of e.g. amino (glycopyranosyl) methanes is thus an important synthetic goal. The amino group would allow linking the C-glycoside to a variety of scaffolds. Our first approach has been to C-link a C-N synthon (HCN or CH 3 NO 2 ) to the anomeric carbon of a natural carbohydrate. We have realized this with cyanide on glycal, on per-O-acetyl sugars and on cyclic acetal protected glycosyl fluorides, prepared by a novel method. The catalytic hydrogenation of glycosyl cyanides presented challenges and new synthetic possibilities. With CH 3 NO 2 , and 4,6-O-alkylidene protected D-glucose or D-mannose derivatives, we obtained very good yields of cyclic Henry condensation products in THF with a novel catalytic procedure. The novel reduction of the resulting nitro (4,6-O-benzylidene-β-D-glycopyranosyl) methane with Fe 0 /Ni 0 in THF/H 2 O/CO 2 readily supplied amino (4,6-O-benzylidene-β-D--glucopyranosyl) methane, derivatives of which were diastereodiversified into D-allo, D-manno, and D-altro C-glycosides. These approaches fail, however, if prerequisite natural carbohydrate precursors are not available in a given case. Thus, a total synthesis scheme was also initiated. Phthalimido acetaldehyde diethylacetal and 4-penten-2-ol, with TiCl 4 , form 2-methyl-4-chloro-6-phthalimido-methyl tetrahydropyran, which was functionalized into phthalimido (6-deoxy-β-D,L-hexopyranosyl) methanes. Chiral extensions of this method are possible. C-'disaccharides' became available from the Ferrier 'dimerisation' of glycals, and from the hydrogenation of glycosyl cyanides.
TL;DR: In this article, the bromide with Cp2TiCl2 and Mn in THF was used to eliminate the acetylated glycosyl bromides to the corresponding glycal.
Abstract: Reductive elimination of acetylated glycosyl bromides to the corresponding glycal is easily achieved by mixing the bromide with Cp2TiCl2 and Mn in THF, and hence does not require the separate preparation of Cp2TiCl using glove-box techniques.
TL;DR: In this paper, differentially protected glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful glycosynyl donors, and an orthogonal coupling strategy using glycoly phosphate donors and thioethyl glycoside acceptors allows for the rapid synthesis of a trisaccharide.
Abstract: Differentially protected glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful glycosyl donors. Activation of β-glycosyl phosphates by TMSOTf at −78 °C achieves the selective formation of β-glycosidic linkages in excellent yields with complete stereoselectivity. Reaction with thiols results in the conversion of glycosyl phosphates into thioglycosides in nearly quantitative yield. An orthogonal coupling strategy using glycosyl phosphate donors and thioethyl glycoside acceptors allows for the rapid synthesis of a trisaccharide.
TL;DR: The DCC mediated coupling reaction of 3,4,6-tri-O -benzyl-1,2-dideoxy-d -arabino-hex-1-enitol gave esters 7a-d in good yield as mentioned in this paper.
Abstract: The DCC mediated coupling reaction of 3,4,6-tri- O -benzyl-1,2-dideoxy- d -arabino-hex-1-enitol ( 5a ) with a variety of sugar based carboxylic acids 6a-d gave esters 7a-d in good yield. Methylenation of the formed esters led to the acyclic enol ethers 8a-d and exposure to the Schrock molybdenum catalyst 1 in warm toluene, in the box, gave the target C -disaccharide glycals 9a-d in good yield. The 1,6-linked gluco based C -disaccharide glycal 9a was converted to the 2-deoxy-β- gluco -derivative 10a and the corresponding and gluco β- gluco-C -disaccharide 13 .
TL;DR: In this paper, a reaction mechanism based on heteroatom abstraction is proposed to give an intermediate glycosyl radical, which reacts with a second equivalent of Ti(III) to yield a glycosyltitanium(IV) species.
Abstract: Glycosyl chlorides and bromides can be rapidly converted to glycals in high yield by reaction with (Cp2Ti[III]Cl)2. This reagent tolerates a wide range of common carbohydrate protecting groups, including silyl ethers, acetals, and esters; the methodology provides a general route for the preparation of glycals substituted with both acid- and base-labile functionality. A reaction mechanism is proposed that is based on heteroatom abstraction to give an intermediate glycosyl radical. This radical reacts with a second equivalent of Ti(III) to yield a glycosyltitanium(IV) species. β-Heteroatom elimination from the glycosyltitanium(IV) complex gives the glycal.
TL;DR: In this article, phenyl 1,2-dithio-α-d-mannopyranoside forms a glycal-1, 2-episulfide, which undergoes controlled oligomerization to afford a family of thio-oligo-α,d-manipyranosides in a single reaction.
Abstract: Under basic conditions, phenyl 1,2-dithio-α-d-mannopyranoside forms a glycal-1,2-episulfide, which undergoes controlled oligomerization to afford a family of thio-oligo-α-d-mannopyranosides in a single reaction. The episulfide can also be intercepted by added thiolates, which leads to other sorts of thioglycosides. These α-(1→2)-linked thio-mannopyranosides might have application as mimics of natural structures such as viral high-mannose glycoproteins or ManLAM.
TL;DR: CMP-3-fluoroneuraminic acid, a useful mechanistic probe for sialyltransferases, has been efficiently synthesized using recent fluorination and phosphorylation techniques from a sialic acid glycal as discussed by the authors.
Abstract: CMP-3-fluoroneuraminic acid, a useful mechanistic probe for sialyltransferases, has been efficiently synthesized using recent fluorination and phosphorylation techniques from a sialic acid glycal.
TL;DR: The cycloadditions produced tricyclic isoxazolidines that represent nonreducing pseudo aza-C-disaccharides stable to hydrolytic conditions.
Abstract: The novel, highly stereoselective, intermolecular cycloaddition reaction of enantiopure cyclic nitrones 8 to 1,2-glycals 9 opens the way to a straightforward synthesis of a broad class of new (1→2)-linked pseudo aza-C-disaccharides 6, suitable substrates for selective inhibition of glycosidase enzymes. The cycloadditions occur with high stereocontrol, displaying preferential interaction between the bottom face of the glycal and the face of the nitrone anti to the substituent on C-3, with the reagents approaching in an exo fashion. The cycloadditions produced tricyclic isoxazolidines 7 that represent nonreducing pseudo aza-C-disaccharides stable to hydrolytic conditions. The target pseudo aza-disaccharides 6 were obtained by sequential deprotection of the hydroxyl groups and isoxazolidine ring-opening.
TL;DR: In this paper, a shorter and more efficient route to 6′-des(N-methyl)sannamycin A and its 2′-epi analog was elaborated with the proven sannamine-type acceptor 10 and the glycosyl donors 5−8 featuring novel protecting patterns.
Abstract: Shorter and more efficient routes to 6′-des(N-methyl)sannamycin A (1) and its 2′-epi analog 2 have been elaborated with the proven sannamine-type acceptor 10 and the glycosyl donors 5–8 featuring novel protecting patterns. With glycal 9 as glycosyl donor (and 10) an expedient access to 2′-desamino- (3) and 2′-desamino-2′-epi-hydroxysannamycin A (4) has been opened. For 4 a modest antibacterial activity was found, while 3 was inactive.