An approach to stereoselective preparation of 3-C-glycosylated d- and l-glucals (original) (raw)
Related papers
Helvetica Chimica Acta, 1994
The triphenylstannyl p-u-glucopyranoside 4 was synthesized in one step from the 1.2-anhydro-a-uglucopyranose 3 with (hiphenylstannyl)lithium (Scheme 1). Transmetallation of 4 with excess BuLi, followed by quenching the dianion 7 with CD,OD gave (1s)-1 ,5-anhydro-3,4,6-triO -benzyl-f 1-2H]-u-glucitol (8) in 81% yield (Scheme 2). Trapping of 7 with benzaldehyde, isobutyraldehyde, or acroleine gave the expected p-Dconfigurated products 11,12, and 13 in good yields. Preparation of C-acyl glycosides from acid chlorides, such as acetyl or benzoyl chloride was not practicable, but addition of benzonitrile to 7 yielded 84% of the benzoylated product 14. Treatment of 7 with Me1 led to 15 (30%) along with 40% of 18, C-alkylation being accompanied by halogen-metal exchange. Prior addition of lithium 2-thienylcyanocuprate increased the yield of 15 to 50% and using dimethyl sulfate instead of Me1 led to 77% of 15. No a-u-anomers could be detected, except with ally1 bromide as the electrophile, which yielded in a 1:l mixture of the anomers 16 and 17. Introduction.-The occurrence as natural products, the biological activity, and the analogy to 0and N-glycosides have led to intense efforts for the synthesis of Cglycosides [ 1-81. Most of these syntheses are based on the reaction of nucleophiles with the electrophilic anomeric center, while syntheses based on an inversion of polarity of the anomeric center are relatively rare [l]. Anomeric monoanions are prone to rapid p elimination [9]. The first successful application of the inversion of polarity of the anomeric center was the chain elongation of doubly deprotonated, 2-hydroxy-1,3-dithianes, derivatives of aldehyde-saccharides [lo]. The first pyranosidic monoanion avoiding pelimination used the weakly reactive anions derived from 1-deoxy-1-nitroaldoses [ 1 1-14]. Reactive glycosyl monoanions usually lack functionality in the 2-position. Such carbanions, based on 2-deoxypyranosides, have been generated by reductive lithiation of 2-deoxy-~-g~ycopyranosyl chlorides [15], phenyl sulfides [ 161, or phenyl sulfones [ 171, by reductive samariation of phenyl sulfones [ 181, by deprotonation of glycals [19-221, and by transmetalation of 2-deoxy-~-glycopyranosylstannanes [23-261 or of the corresponding alkenylstannanes [23-261.
]A potentially versatile synthesis of glycosides
Carbohydrate Research, 1973
Phenyl I-thio-D-glucopyranosides in the presence of mercury(H) salts are readily solvolysed to give all@ D-glucopyranosides with inverted anomeric configuration. Methanolyses of the #? and CI anomers afford the methyl tl-and p-glycosides which were isolated in yields of 74 and 87%, respectively; n.m.r. examinations indicated that, whereas the /?-glycoside was produced stereospecifically, the a-glycoside was formed together with-6% of its /I isomer. The approach can be extended to the synthesis of complex glycosides (the a anomers of which are of special interest) as was illustrated by the preparation of cholestanyl and 1-naphthyl a-o-glucopyranoside and a disaccharide derivative.
Carbohydrate Research, 1988
In a previous paper in this series2, we outlined our interest in the synthesis of some oligosaccharides containing ~-fume a-(1+3)-link4 to 2-acetamido&deoxy-~glucose. Our interest in this class of compounds was, to a large extent, motivated by a desire to obtain reference compounds in studies related to (1+3)-CAL-fucosyltransferase. This interest was, however, enhanced by recent reports associating a variety of such oligosaccharide suuctures with certain types of human ca11cers3-~.
ChemInform, 1994
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Stereoselective synthesis of [13C]methyl 2-[15N]amino-2-deoxy-β-d-glucopyranoside derivatives
Carbohydrate Research, 2001
Efficient syntheses of three [ 13 C]methyl 2-[ 15 N]amino-2-deoxy-b-D-glucopyranoside derivatives are described. Amination of the D-glucal with (saltmen)Mn(15 N) proceeded with 11:1 stereoselectivity favoring the gluco configuration; subsequent methylation of the [ 15 N]lactol using [ 13 C]iodomethane and silver(I) oxide afforded the doubly labeled b glucoside in high yield. This compound served as the common precursor for three [ 13 C]methyl 2-[ 15 N]aminoglucosides: (2-[ 15 N]trifluoroacetyl-), (2-[ 15 N]acetyl-), and (2-[ 15 N]azido-). Selected heteronuclear coupling constants are reported.
Carbohydrate Research, 2007
Michael addition of 1,2:3,4-di-O-isopropylidene-6-thio-alpha-D-galactose (2) to 2-propyl 6-O-acetyl-3,4-dideoxy-alpha-D-glycero-hex-3-enopyranosid-2-ulose (1) afforded, as the major diastereoisomer, 2-propyl 6-O-acetyl-3-deoxy-4-S-(6-deoxy-1,2:3,4-di-O-isopropylidene-alpha-D-galactopyranos-6-yl)-4-thio-alpha-D-threo-hexopyranosid-2-ulose (3, 91% yield). Reduction of the carbonyl group of 3, followed by O-deacetylation gave the two epimers 7 (alpha-D-lyxo) and 8 (alpha-D-xylo) in a 1:2 ratio. On removal of the protecting groups of 8 by acid hydrolysis, formation of an 1,6-anhydro bridge was observed in the 3-deoxy-4-thiohexopyranose unit (10). The free non-glycosidic thioether-linked disaccharide 3-deoxy-4-S-(6-deoxy-alpha,beta-D-galactopyranos-6-yl)-4-thio-alpha,beta-D-xylo-hexopyranose (11) was obtained by acetolysis of 10 followed by O-deacetylation. A similar sequence starting from the enone 1 and methyl 2,3,4-tri-O-benzoyl-6-thio-alpha-D-glucopyranoside (12) led successfully to 2-propyl 3-deoxy-4-S-(methyl 6-deoxy-alpha-D-glucopyranos-6-yl)-4-thio-alpha-D-lyxo-hexopyranoside (17) and its alpha-D-xylo analog (19, major product). In this synthetic route, orthogonal sets of protecting groups were employed to preserve the configuration of both reducing ends and to avoid the formation of the 1,6-anhydro ring.
THE SYNTHESIS OF MEDICINALLY IMPORTANT PHARMA MOLECULES FROM CARBOHYDRATES BUILDING BLOCKS
Mukesh Chander, 2023
The carbohydrate molecules forms a variety of natural products named "glycoconjugateskey components of different biological processes". The challenge lies in preparation of bulk quantities of these organics for industrial application and processes. The monosaccharide as raw material to synthesize glycoconjugates are available in large quantities so as to oligomerise these monosaccharides.The chiral nature of monosaccharide has made them suitable to use as starting material also for the synthesis of compounds other than glycoconjugates. Glycal a cyclic enol ether derivatives of sugars can be formed as pyranose (six-membered) or furanose (five-membered) rings, depending on the monosaccharide used as a starting material to synthesize the glycal which can be transformed to an exo-glycal. More recently, glycals have also been shown to be excellent starting substrates for library development and preparation of exo-glycals. The Fischer-Zach method has been one of the most popular methods for synthesizing glycals. It has been suggested that heterolytic cleavage of the carbon-halogen bond occurs under these acidic conditions ,initially to give an anomeric carbocation that, after taking two electrons from the zinc atom, generates a transient carbanion that evolves through the splitting off of an acetate anion. In present study we have investigated the role of other reducing agents in this transformation with glycosyl halides include sodium and potassium metal, sodium naphthalide, zinc/silver graphite, aluminum amalgam, SmI2, potassium graphite ,lithium/ammonia, chromium(II), zinc/base, cobalt(II), and titanium(III). A glucal derivative has also been prepared by introduction of a halogen atom at C-2, followed by a reductive elimination reaction in the opposite sense.
A General Strategy for Stereoselective Glycosylations
Journal of the American Chemical Society, 2005
The principal challenge that the synthesis of oligosaccharides of biological importance presents is the development of a general approach for the stereoselective introduction of a glycosidic linkage. It is shown here that a (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety at C-2 of a glycosyl donor can perform neighboring group participation to give a quasi-stable anomeric sulfonium ion. Due to steric and electronic factors, the sulfonium ion is formed as a trans-decalin ring system. Displacement of the sulfonium ion by a hydroxyl leads to the stereoselective formation of R-glycosides. NMR experiments were employed to show convincingly the presence of the-linked sulfonium ion intermediate. The (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety could be introduced by reaction of a sugar alcohol with acetic acid (1S)-phenyl-2-(phenylsulfanyl)ethyl ester in the presence of BF3-OEt2. Furthermore, it could be removed by conversion into acetate by treatment with BF3-OEt2 in acetic anhydride. The introduction as well as the cleavage reaction proceeds through the formation of an intermediate episulfonium ion. The use of the new methodology in combination with traditional neighboring group participation by esters to introduce-glycosides makes it possible, for the first time, to synthesize a wide variety of oligosaccharides by routine procedures. The latter was demonstrated by the synthesis of the Galili trisaccharide, which has been identified as an epitope that can trigger acute rejections in xeno-transplantations, by the one-pot two-step glycosylation sequence.