Epimerization prevention

Enamines, too, react with quinone methides. It is suggested that a charged intermediate is involved in which, in substituted analogues, epimerization prevents the formation of diastereoisomers (70JHC1311). 

GDP-mannuronate is the activated precursor that donates M residues to mannuronan. The proteins required for this step are localized in the inner membrane and subsequent transformations of the incipient alginate occur in the periplasmic space. The final steps of alginate synthesis are epimerization and acetylation. These transformations are not carried out at every residue. Epimerization occurs at C5, converting a /3-D-mannuronate residue to a ci-L-guluronate residue. The number and pattern of distribution of G residues in mature alginate differs across species. Acetylation occurs at 02 or 03, and only on M residues. Acetylation and epimerization appear to be mutually exclusive, such that acetylation precludes epimerization and epimerization prevents acetylation. Secretion of mature alginate is mediated by AlgE, a porin-like protein. 

This reaction was run in the presence of the triplet quencher 1,3-pentadiene to prevent epimerization due to a-cleavage (a triplet reaction). 

The existence of a protonated oxazolone has been demonstrated indirectly by a simple experiment. When p-nitrophenol was added to an excess of 2-alkoxy-5(4//)-oxazolone in dichloromethane, a yellow color appeared. The color persisted until all the p-nitrophenol had been consumed by the oxazolone. The anion of p-nitro-phenol is yellow. The explanation for the color of the mixture is the presence of the p-nitrophenoxide anion that was generated by abstraction of the proton by the oxazolone. In summary, protonation of the O-acylisourea suppresses the side reaction of oxazolone formation as well as the side reaction of A-acylurea formation and accelerates its consumption by enhancing its reactivity and generating an additional good nucleophile that consumes it. Protonation of the oxazolone suppresses epimerization by preventing its enolization and also increases the rate at which it is consumed.4 68 78 79... 

Epoxyketone 60 has also been prepared by hydroxyselenation of 4-acetyl-1-methylcyclohexene with phenylselenium chloride and water, oxidation of the selenide to selenoxide with buffered aqueous oxone, and elimination of the se-lenoxide in the same pot to provide the epoxide [80]. Control of the conditions was essential to prevent epimerization of the ketone. This route has little to recommend it given the expense and toxicity of the reagents, the moderate yield, and the problems with epimerization. 

The first three of these agents to be discovered, tetracycline (1)chlortetracycline (2), and oxytetracycline (3), are subject to two major modes of degradation under conditions occurring during their isolation, purification, formulation, and administration. These are dehydration and epimerization. Each of these reactions leads to inactivation of the antibiotic thus, considerable effort has been expended in attempts to prevent or minimize these reactions. 

To neutralize the hydrolysis products the solution is passed through a column (of about 15-cm length and 1-cm width) packed with an anion exchanger (e.g.,anion exchanger from Example 5-10). Neutralization with alkaline earth metal carbonates is to be avoided at all costs, in order to prevent epimerization of glucose to mannose which is favored by complex formation between mannose and alkaline earth metal ions. 

The use of the C-terminal esters imposes two synthetic hurdles (1) efficient and racemi-zation-free attachment of the C-terminal amino acid ester to the resin by its side-chain functionality and (2) prevention of C-terminal epimerization both during chain assembly and cyclization. 

The reactivity of the nitroalkenes has been tested in the reaction with 1-thiosugars via conventional Michael reactions catalyzed by triethylamine. In both cases the stereoselective 1,2 addition proceeds by exclusive formation of an exo-adduct via formation of an S-linkage from the less hindered face of the molecule. As expected, the shielding effect of the 1,6-anhydro bridge effectively prevents the formation of the 2-equatorial product, yielding only the 2-axial products with a new quaternary center at C-2. This provides a stable molecule, as no epimerization or p-elimination is observed during the reduction of the nitro group. 

As discussed previously for the MBH reaction, the aza-MBH reaction involves rate-limiting proton transfer in the absence of added protic species (Scheme 5.22) [93]. In contrast to the MBH reaction, however, the aza-MBH exhibits no autocatalysis. Bronsted acidic additives lead to substantial rate enhancements through acceleration of the elimination step. It has been shown that phosphine catalysts - either alone or in combination with protic additives - may trigger epimerization of the aza-MBH product by proton exchange at the stereogenic center. This fact indicates that the spatial arrangement of a bifunctional chiral catalyst in this reaction is crucial not only for the stereodifferentiation within the catalytic cycle but also to prevent subsequent epimerization. 

An intramolecular radical cyclization on carbohydrate derivatives was the method developed by Lundt and Homeman in a highly stereocontrolled synthesis of functionalized cyclopentanes [9]. Due to the neutral conditions required for the cyclization step, which prevented competing side reactions such as P-elimination and base-promoted epimerization, the potential of the employed radical intramolecular reaction versus the classical carbanionic carbon-carbon bond forming reactions was demonstrated. 

In Figure 14(b), the combination of proline and 2-aminomethyl pyrrolidine, the asymmetric transformation was observed but no preferential crystallization occurred. In Figure 14(c) only racemization was observed. Moreover, in Figure 14(d), non-coplanarity of the iminazoline and a-branched carbon prevented the double-bond shift and epimerization did not occur. 

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