Tagatose formation

An advantage of these enzymes is that they are stereocomplementary, in that they can synthesize the four possible diastereoisomers of vicinal diols from achiral aldehyde acceptors and DHAP (Scheme 4.2). Although this statement is generally used and accepted, it is not completely true since tagatose-l,6-bisphosphate aldolase (TBPA) from Escherichia coli-the only TBPA that has been investigated in terms of its use in synthesis-does not seems to control the stereochemistry of the aldol reaction when aldehydes different from the natural substrate were used as acceptors [7]. However, this situation could be modified soon since it has been demonstrated that the stereochemical course of TBPA-catalyzed C—C bond formation may be modified by enzyme-directed evolution [8]. 

Two new stereocenters are established in the DHAP-dependent aldolases-cata-lyzed carbon-carbon bond formation. Consequently four different stereoisomers can be formed (Scheme 5.23). Enantioselective aldolases that catalyze the formation of just one of each of the stereoisomers are available fructose 1,6-diphosphate aldolase (FDP A), rhamnulose 1-phosphate aldolase (Rha 1-PA), L-fucu-lose 1-phosphate aldolase (Fuc 1-PA) and tagatose 1,6-diphosphate aldolase (TDP A). In particular the FDP A, that catalyzes the formation of the D-threo stereochemistry, has been employed in many syntheses. One such FDP A that... 

Horvat, S., Roscic, M., Varga-Defterdarovic, L., Horvat, J. Intramolecular rearrangement of the monosaccharide esters of an opioid pentapeptide formation and identification of novel Amadori compounds related to fructose and tagatose. J. Chem. Soc., Perkin Trans. 1 1998, 909-914. 

S. Passeron and E. Recondo, Dicyclohexylcarbodi-imide a new agent for carbohydrate epimer-ization and isomerization. Part I. Psicose formation, J. Chem. Soc., (1965) 813-81 R. Griinnagel and H. J. Haas, Darstellung von D-Tagatose, Ann., 721 (1969) 234-235. 

Ribofuranosyl derivatives of substituted benzimidazoles have been found to have virus inhibitory activity (44)-From glucosone, compounds with quinoxaline structures may be produced (4S), In the presence of hydrazine and o-phenylenediamine, 1-deoxy-1-p-toluino-D-fructose or -D-tagatose is converted to a quinoxaline compound in the pH range 6 to 8 by a mechanism similar to osazone formation 46),... 

On treatment with molybdic acid, in addition to the primary C-2 epimeric products, the C-4, C-5 threo aldoses also similarly provide the complementary C-3 epimers. However, a proportion of these C-2, C-3 diastereoisomers, especially idoses and to some extent guloses and taloses, are transformed into more stable 2-ketoses, namely to sorboses and tagatoses in the case of hexoses [9] and their 6-deoxy derivatives [6] or to g/uco-glyco-2-uloses and mawwo-glyco-2-uloses in the case of higher aldoses [6,13]. The formation of these 2-ketoses from their parent aldoses is not associated with the molybdate catalysis and is obviously ascribed to the general acidity [41] of the reaction medium. 

Molybdic acid catalyzed isomerization of D-tagatose (without boric acid) provided a 19 1 ratio (as estimated by NMR spectroscopy) of the ketose and 2-C-(hydroxymethyl)-D-xylose. Surprisingly, D-psicose on treatment with molybdic acid under otherwise identical reaction conditions, even after prolonged reaction times, did not lead to the formation of 2-C-(hydroxymethyl)-D-arabi-nose as expected. The co-application of boric acid, either in this case or in the case of D-tagatose, does not shift the equilibria towards the corresponding 2-C-hydroxymethyl)aldoses. 

To summarize the mechanistic and structural studies with hex-2-uloses and 2-C-(hydroxymethyl)pentoses performed under the conditions of the Bflik reaction, the following conclusion can be made. Molybdic acid catalyzes two types of interconversions between the sugars shown in Scheme 13. D-Fructose (17), d-sorbose (21) and D-tagatose (29) when treated with the catalyst are subjected to highly stereospecific carbon-skeleton rearrangements to produce thermodynamic equilibrium mixtures with the respective 2-C-(hydroxymethyl)-D-ribose (D-hamamelose, 20), 2-C-(hydroxymethyl)-D-lyxose (30), and 2-C-(hydroxymethyl)-D-xylose (31). (For simplicity, all the sugars are represented in their acyclic non-hydrated forms in spite of which some of their interconversions proceed in the acyclic hydrated structures, while others proceed in cyclic hemiacetal ones. All of the interconversion relationships are schematically represented in the d series, despite the fact that some of them were experimentally performed with the L series.) Probably because of extensive formation of unproductive com-... 

Miethchen and co-workers have published a number of papers concerning the use of chloral and dicyclohexylcarbodiimide (DCC) as a means to invert configuration of chiral centres in carbohydrates. These reagents were found to react with his-vicinal triols with a cis, trans sequence of hydroxyl groups and this resulted in the formation of cyclic acetals in which the central atom of the triol had been inverted. For example, the rare monosaccharide o-tagatose has been easily prepared from D-fructose (Scheme 4) [6]. Concerning the mechanism of this reaction, chloral and DCC react with fructose derivative 10 to give intermediates 11 and 12. The latter mentioned intermediate then reacts intra-molecularily in an SN2-type reaction as shown. This furnished product 13 in 59% yield. 

Engvall, E. and Perlmann, P. Enzyme-linked inununosorbent assay (ELISA) Quantitative assay of immunoglobulin G. Immunochemistrv 1971.8, 871-874. Adachi, S. Formation of lactulose and tagatose from lactose in strongly heated milk. Nature 1958 181, 840-841. 

Efficient procedures for the conversion of levoglucosenone to rare sugars, e.g., D-altrose, D-allose, 4-deoxy-o-mannose, have been devised. Hydrolytic opening of the L-sorbopyranose-derived epoxide 12 with nucleophilic attack at C-4 was the key-step in the transformation of L-sorbose to L-fructose, which requires inversion of configuration at C-3 and C-4. The formation of D-tagatose from d-... 

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