Keto sugars

Figure 2 Formation of l-amino-2-keto sugars from aldose sugar...

A. M. Griffin, N. J. Newcombe, D. Alker, M. V. J. Ramsay, and T. Gallagher, 2-Keto sugars as preformed heterocyclic building blocks synthetic studies, Heterocycles, 35 (1993) 1247-1258. 

Transfer of a two-carbon unit from a 2-keto sugar to the carbonyl carbon (Ci) of an aldose by a transketolase, which requires thiamine pyrophosphate and magnesium as cofactors. A covalent enzyme-substrate intermediate is formed similar to the one that occurs during the pyruvate dehydrogenase reaction (Chapter 13). 

Addition of dialkyl phosphites to 3-nitro-2,3-dideoxyhexenopyranose (11 ), or 1,2-dideoxyhexenopyranose (12) gives rise to phosphonates. An alternative route to sugar phosphonates involves the addition of dialkyl phosphites to 2-keto-sugars. ... 

The enzyme is a transketolase and the process is called transketolation (keto-carrying). Transketolase uses thiamin diphosphate as a coenzyme to bring about the transfer of a 2-carbon unit from one sugar (a 2-keto sugar) to aldoses (monosaccharides with the characteristic aldehyde group [-CHO]). 

Fortunately, the oxidation of l,2 5,6-di-0-isopropylidene-a-D-glucofura-nose to l,2 5,6-di-0-isopropylidene-a-D-nfoo-hexofuranos-3-ulose (1) can be accomplished using either phosphorus pentoxide (10, 44) or acetic anhydride (10, 52) in methyl sulfoxide although this oxidation is effected with ruthenium tetroxide (6,7, 46), it is exceeding difficult with other oxidizing agents (53). Keto-sugar 1 is reduced stereospecifically... 

C. Miscellaneous.—Among ylides, PhsP CHR, used in conventional olefin synthesis with protected keto-sugars are those with R = H, CN, SMe, and COR. ... 

PCC in the presence of 4 A MS to afford the corresponding keto sugars (175, 176), which after Tebbe methylenation led to the corresponding exoglycals, valuable intermediates for the synthesis of C-disaccharides. Dondoni el al.159 made use of PCC in the presence of powdered 4 A MS to introduce suitable formyl groups in the carbohydrate, and allowing the synthesis of >6)-linked oligosaccharides,... 

Ketose Sugar N-Fructosylamine (if ketose is fructose) Enol 2-Amino-l-Keto Sugar... 

Figure 3 Formation of 2-amino-1-keto sugars from ketose sugar...

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

The endo-spiro-OZT could be prepared through a reaction sequence similar to that applied for the exo-epimer, with spiro-aziridine intermediates replacing the key spiro-epoxides (Scheme 18). Cyanohydrin formation from ketones was tried under kinetic or thermodynamic conditions, and only reaction with the d-gluco derived keto sugar offered efficient stereoselectivity, while no selectivity was observed for reaction with the keto sugar obtained from protected D-fructose. The (R) -cyanohydrin was prepared in excellent yield under kinetic conditions (KCN, NaHC03, 0 °C, 10 min) a modified thermodynamic procedure was applied to produce the (S)-epimer in 85% yield (Scheme 18). 

OZTs from keto sugars. An original approach for the synthesis of OZTs from carbohydrate-based a-hydroxyketones was recently published by Silva et al.4Sa who investigated the reactivity of carbohydrate-based a-hydroxyketone in the presence of thiocyanic acid. 

Aminosugars are the result of replacement of one or more hydroxyl groups in a sugar by amino groups. They are formed in nature by transamination processes (see Section 15.6) on appropriate keto sugars, which are themselves the product of regiospecific... 

A slightly different acyl anion equivalent is transferred in transketolase reactions, and this anion is then used in a subsequent aldol reaction. TVansketolase removes a two-carbon fragment from keto sugars... 

Many DOHs, such as L-daunosamine, L-epivancosamine or L-ristosamine, contain an amino group at C3, which is introduced by an aminotransferase. The substrate for this reaction is the 3-keto sugar intermediate that arises as a consequence of the action of a 2,3-dehydratase. This transaminahon reaction has been biochemically characterized in the biosynthesis of L-epivancosamine [10]. Using a coupled reaction with EvaB (2,3-dehydratase) and EvaC (aminotransferase), with pyridoxal-5-phosphate (PEP) as a coenzyme and L-glutamate as a cosubstrate, they were able to show conversion of TDP-4-keto-2,6-dideoxyglucose into thymidine-5 -diphospho-3-amino-2,3,6-trideoxy-D-threo-hexopyranos-4-ulose. 

Based on the stereospecific transketolase-catalyzed ketol transfer from hydroxy-pyruvate (20) to D-glyceraldehyde 3-phosphate (18), we have thus developed a practical and efficient one-pot procedure for the preparation of the valuable keto-sugar 19 on a gram scale in 82% overall yield [29]. Retro-aldolization of D-fructose 1,6-bisphosphate (2) in the presence of FruA with enzymatic equilibration of the C3 fragments is used as a convenient in-situ source of the triose phosphate 18 (Scheme 2.2.5.8). Spontaneous release of CO2 from the ketol donor 20 renders the overall synthetic reaction irreversible [29]. 

The two most common functional groups found in monosaccharides (in open chain form) are aldehyde and ketone. When a monosaccharide contains an aldehyde, it is known as an aldose, e.g. glucose, and in the case of ketone, it is called a ketose or keto sugar, e.g. fructose. 

Several reviews describing methods for oxidation of carbohydrates leading to the corresponding aldehydo and keto sugars have appeared.18-22 Also, a short discussion published in 1970 was devoted to... 

The synthesis of type III branched-chain sugars is based mainly on the use of ketosugars treated under Wittig-type conditions (see path a, Scheme 4) [13]. Several other methods, such as aldolization-crotonization or direct alkylidenation at the a-position of the carbonyl group of a keto sugar have been developed (path b). 

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