Glyceraldehyde preparation

NeuA, has broad substrate specificity for aldoses while pyruvate was found to be irreplaceable. As a notable distinction, KdoA was also active on smaller acceptors such as glyceraldehyde. Preparative applications, for example, for the synthesis of KDO (enf-6) and its homologs or analogs (16)/(17), suffer from an unfavorable equilibrium constant of 13 in direction of synthesis [34]. The stereochemical course of aldol additions generally seems to adhere to a re-face attack on the aldehyde carbonyl, which is complementary to the stereoselectivity of NeuA. On the basis of the results published so far, it may be concluded that a (31 )-configuration is necessary (but not sufficient), and that stereochemical requirements at C-2 are less stringent [71]. 

An efficient asymmetric total synthesis of L-fructose combines the Sharpless asymmetric dihydroxylation with an enzyme-catalyzed aldol reaction. L-Glyceraldehyde, prepared from acrolein, is condensed to DHAP in a buffered water suspension of lysed cells of KI2 Escherichia coli containing an excess of L-rhamnulose-1-phosphate (Rha) aldolase E. coli raised on L-rhamnose as sole carbon source). The L-fructose phosphate obtained is hydrolyzed to L-fructose with acid phosphatase. Similarly, the RAMA-catalyzed condensation of D-glyceraldehyde with DHAP,... 

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

Figure 10.46 Application of ThrA catalysis for the stereoselective synthesis of dihydroxyprolines from glyceraldehyde, and an adenylamino acid for RNA mimics (a). ThrA based preparation of precursors to the immunosuppressive lipid mycestericin and the antibiotic thiamphenicol (b).

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

The dipolar cycloadditions of nitrone (—)-353 prepared from protected glyceraldehyde 347 (Scheme 74), to dipolar-ophiles 354, 356, and 358 afforded the heterocycles 355, 357, 359-361, respectively (Table 14) <2005JOC3157>. 

Periodate oxidation of 5,6-O-isopropylidene-L-gulono-1,4-lactone (9a) gave 2,3-O-isopropylidene-L-glyceraldehyde in 69% yield. This compound was used to prepare 2,3-O-isopropylidene-L-glycerol and it was also condensed with amines and Wittig reagents (34). 

In order to test these assumptions Heathcock prepared different chiral ketones. Thus, the aldol condensation of the fructose-derived ketone and the acetonide of (/ )-glyceraldehyde gave poor results in the double stereodifferentiation, since an almost equal mixture of the two jyn-aldols 68a and 68b were obtained. However, the reaction with the (5)-aldehyde gave only one syn adduct (69a) (Scheme 9.22) ... 

L-Ribose is quite rare and the only practical method for its preparation is the transformation of L-arabinose by the method of Austin and HumoUer (4 steps, 9.5 % overall yield). L-Ribose has also been derived from, 2,3-<9-isopropylidene-L-glyceraldehyde, (5 steps, 12 %) after separation from a mixture containing L-arabinose. In Scheme 7 we summarize our total syntheses of D- and L-ribose derivatives using the " naked sugars" 32 and 38, respectively." Ketone 138 (Scheme 4) was oxidized into the corresponding lactone (-)-158 with MCPBA in 98 % yield. Treatment with anhydrous methanol, 2,2-dimethoxypropane and a small amount of methanesulfonic acid afforded the methyl 5-deoxy-D-allonate (-)-I59... 

Last year, a short enantioselective total synthesis of herbarumin III (42) in 11% overall yield was published the approach applied uses Keck s asymmetric allylation and Sharpless epoxidation to build the key fragment. Esterification with 5-hexenoic acid and a RCM was used to yield 42. Finally, another asymmetric synthesis of herbarumin III (42) was carried out using (R)-cyclohexylidene glyceraldehyde as the chiral template. The key steps of the synthesis were the enantioselective preparation of the... 

L-Mannitol has been prepared by the reduction of L-mannosaccharo-dilactone or L-mannose. By far the most convenient procedure is that used by Baer and Fischer for their preparation of L-glyceraldehyde by the oxidative cleavage of l,2 5,6-diisopropylidene-L-mannitol with lead tetraacetate. L-Arabinose was converted to L-mannonolactone by the cyanohydrin synthesis and this was hydrogenated over platinum oxide to the desired L-mannitol. High hydrogen pressures, rather than low as usually employed with this catalyst, were used. 

Gemcitabine (Gemzar ) is prepared from the 2,2-difluoro-2-deoxyribose, itself available by the addition of the Reformatsky reagent of ethyl bromodifluoroace-tate on the (R)-2,3-0-isopropylidene glyceraldehyde. The condensation of the corresponding mesylate with di(trimethylsilyloxy)pyrimidine provides gemcitabine [93]. The control of the stereoselectivity of the Reformatsky reaction is difficult (Fig. 30) [95]. Other approaches involving the fluorination of D-pyranoses have been proposed (Fig. 31) [96]. 

Fluorination of the nucleoside has also failed, providing very low yields. In consequence, 3,3-difluoro-2,3-dideoxyfuranoses and the related nucleosides are generally prepared by fluorination of 2,3-dideoxyfuranoses. However, the latter has to be prepared with a large number of steps from a natural precursor, such as L-xylose (Figure 6.10). " Some total syntheses of 3,3-difluoro-2,3-dideoxyfuranoses have been performed from glyceraldehyde (Figure 6.10). ... 

Fluorofuranose precursors are prepared via Horner-Emmons reaction on L-glyceraldehyde acetonide (Figure 6.11). Due to the allylic position of the base, these compounds are much more unstable than the related saturated molecules (cf. Figure 3.17, Chapter 3). The presence of the fluorine atom enhances the hydrolytic stability of these compounds. Some of these molecules have good antiviral activities on infected cells. 

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