Glyceraldehyde, stereoselective

Higher degrees of induced stereoselectivity emerge from the reactions of (/ )-glyceraldehyde acetonide with several enolates. For example, a single diastereomeric adduct results from the reaction of the acetonide with the lithium enolate of pinacolone4. 

Moderate stereoselectivity (80 20) was observed in the potassium fluoride catalyzed Henry reaction of nitromethane with isopropylidenc-D-glyceraldehyde (10). The major product could be separated from the mixture by fractional crystallization9. 

Aqueous cycloaddition using glyco-organic substrates. Facial stereoselectivity in Diels-Alder reactions of a chiral diene derived from D-glyceraldehyde [102]... 

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]. 

Aldehydes up to a chain length of four nonhydrogen atoms are tolerated as acceptors. 2-Hydroxyaldehydes are relatively good acceptors, and the D-isomers are preferred over the t-isomers [180]. Reactions that lead to thermodynamically unfavorable structures may proceed with low stereoselectivity at the reaction center [181]. Recently, a single-point mutant aldolase was found 2.5 times more effective than the wild type in accepting unphosphorylated glyceraldehyde [182,183]. 

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).

Detailed studies have been carried out on the stereoselectivity of a- and -substituted aldehydes toward the tartrate boronates.47 a-Benzyloxy and (3-benzyl oxy-a-methylpropionaldehyde gave approximately 4 1 diastereoselectivity with both the R, R- and S, S- enantiomers. The stereoselectivity is reagent (tartrate) controlled. The acetonide of glyceraldehydes showed higher stereoselectivity. 

Addition of the lithium salt of tris(triphenylthio)methane to the D-glyceraldehyde-derived nitroolefin 80 resulted in a stereoselective Michael addition leading to adduct 81, which was then converted into the novel... 

Recently, two more stereoselective cases of bromine-lithium exchange reactions have been observed. Both the glyceraldehyde-derived bromoalkene 45 and lactaldehyde-derived 47 yield the -configurated lithium carbenoids 46 and 48, respectively, when treated with... 

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]. 

H. Chikashita, T. Nikaya, and K. Itoh,.Iterative and stereoselective one-carbon homologation of 1,2-O-cyclohexylidene-D-glyceraldehyde to aldose derivatives by employing 2-lithio-l,3-dithiane as a formyl anion equivalent, Nat. Product Lett. 2 183 (1993). 

The same double stereoselection was observed by Young and coworkers when both enantiomers of the glyceraldehyde acetonide were reacted with the lithium enolate of pyroglutamic esters. The (Tf)-enantiomer gave only the (5,5) adduct while the (5)-enantiomer gave a mixture of diastereomers (Scheme 121)576. 

DHAP (A) is used in nature as a C3-methylene component for the efficient and stereoselective formation of carbohydrates (Scheme 1). In this pathway DHAP reacts with D-glyceraldehyde-3-phosphate (1) via an enzyme-catalyzed aldol reaction to form 2. After dephosphonyla-tion the aldol adduct 3 is then transformed to various carbohydrates and derivatives (Calvin 1962). 

As described here, both enantiomers of 3 can be prepared In three steps from commercially available diethyl D- and L-tartrate in up to 70% over-all yield.2 3 5 Procedures to obtain the benzylidene acetal,11 12 with the ensuing reduction step,11. 2 are based on previous literature reports. Both enantiomers of 3 have been used in highly stereoselective nitroaldol additions.3 13 Imines, nitrones, oximes, and nitrile oxides derived therefrom were recently employed in a variety of additions/cycloadditions.14 15 (-)-2-0-Benzyl-L-glyceraldehyde has further been used... 

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