Anomer kinetical

Reaction of 3-amino-1-propanol and 5-bromo-5-deoxy-D-furanoxylose (25) in D2O was monitored by NMR (Scheme 4). The a-anomer of trihydroxypyridoPd-f l-LbSloxazine 26 formed 20 times faster, but the /3-anomer 27 was more stable (A / 7.3). The faster formation of the Q -anomer is a consequence of a kinetic anomeric effect that destabilizes the transition state for equatorial A -alkylation and formation of the /3-anomer 27 (OOJOC889). 

For a distinction in the binding mode of substrate constitutional isomers, we first focused on the synthesis of the structurally related anhydroalditol derivatives 7 and 8 as potential inhibitors of FucA that lack the anomeric hydroxyl group of the natural substrate 5 and thus ehminate the possibility for ring opening and cleavage [12] (Scheme 2.2.5.3). Fucitol 1-phosphate 10 was included in the study as a potential mimic of the open-chain form. From kinetic data it became obvious that the aldolase binds preferentially a cyclic substrate, and selectively the more abundant P-anomer of the natural substrate that correlates with 7. 

A kinetic study of the methyl glycosidation of D-mannose was also made by Mowery.48 The more stable anomer, the a-D-mannofuranoside, was formed at a higher initial rate (see Table III) the proportions of both furanosides in the final equilibrium mixture was too small to permit accurate comparison of isomer distribution. The conformational stability of the D-mannofuranosides may be compared with that of the D-lyxo-furanosides the furanoid structures are similar, except for the bulky two-carbon group at 04 of the hexoside. This similarity is shown in the very small proportion of n-lyxofuranosides (see Table V) and of D-manno-furanosideo (see Table III) in the final equilibrium mixtures, and also in the initial formation of D-mannopyranosides48 and of D-lyxofuranosides.u... 

The formation of the tranu-l, 2-glycofuranosides is effected in neutral solution, where anomerization cannot occur. Treatment of 3,4-O-isopropyl-idene-2,5-di-O-methyl-L-rhamnose diethyl dithioacetal with mercuric chloride in boiling methanol gave" a 61% yield of the -L-furanoside no trace of the 0-l anomer was found. In this experiment, with an acidic solution (no mercuric oxide present), anomerization could have led to the formation of the more stable anomer. In the normal reactions cited, with maintenance of a neutral solution, no anomerization can occur, and yet the more stable anomer, presumably the kinetic product, is still the major anomer formed. 

The enzyme has been shown to be specific for the (3 form by rapid reaction measurements on a time scale faster than that for the interconversion of the anomers, and also by determination of the activity toward model substrates that are locked in either of the configurations. By using sufficient enzyme to phos-phorylate all the active anomer of the substrate before the two forms can reequilibrate, it is found that 80% of the substrate reacts rapidly, and that the remaining 20% reacts at the rate constant for the anomerization. The kinetics were followed both by quenched flow using [y-32P]ATP10 and by the coupled spectrophotometric assay of equation 6.4.11 The other evidence comes from the steady state data on the following substrates 12... 

Analysis of Freshly Cyclized 2,3-di-O-methyl-D-arabinose. The system 3,4-di-O-methyl-D-mannitol (2)—sodium metaperiodate meets the foregoing specifications. 3,4-Di-O-methylmannitol was rapidly cleaved by periodate to 2,3-di-O-methyl-D-arabinose (3), which is resistant to further oxidation (19). We prepared the crystalline / -anomer of this sugar (the a-anomer had previously been crystallized (20)) and showed that on a suitable GLC column the trimethylsilyl derivatives of the four ring forms could be separated (Figure 9). The individual peaks were characterized by preparative GLC and mass spectrometry. This allowed the analysis of the mixtures of anomeric forms generated in kinetic experiments (see p. 34). 

HI hi acetic acid allows the reduction of jS-peracetates of the higher sugar N-acetylneuraminic acid to the corresponding anomeric deoxy compounds.277 At room temperature this method gave exclusively the a-anomer, whereas at —20 °C a 4 1 a [i ratio resulted. This may be explained by thermodynamic and kinetic protonation of ester enolates generated in situ from anomeric iodide in a manner reminiscent of previous reductions of 2-iodo sugar lactones.278... 

One can manage the formation of the kinetical (5- or the thermodynamical -anomer by means of different reaction protocols. 

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