Oxocarbenium-like transition state

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

Lysozyme catalyzes the hydrolysis of the polysaccharide component of plant cell walls and synthetic polymers of j8(l — 4)-linked units of A-acetylglucosamine (NAG) (Chapter 1). It is expected from studies on nonenzymatic reactions that one of the intermediates in the hydrolytic reaction is a oxocarbenium ion in which the conformation of the glucopyranose ring changes from a full-chair to a sofa (half-chair) conformation (Chapter 1). The transition state analogue I, in which the lactone ring mimics the carbonium ion-like transition state n, binds tightly to lysozyme = 8.3 X 10 8M.10... 

Sialosides have a distinct mechanism of hydrolysis for its unusual sugar structure of sialic acid. For example, the large 8-dideuterium and small primary kinetic isotope effects observed at the anomeric carhon and the large secondary kinetic isotope effect observed at the carboxylate carbon in the acid-catalyzed solvolysis of CMP-Af-acetyl neuraminate 24 support an oxocarbenium ion-like transition state 25 having the 5S conformation without nucleophilic participation of carboxylate and with the carboxylate anion in a looser environment than in the ground state [15] (O Fig. 3). Such a zwitterion structure is consistent with the results from calculations using the COSMO-AMI method for aqueous solutions [16]. 

CMP-lV-acetyl neuraminic acid and oxocarbenium ion-like transition state in sialoside hydrolysis... 

The mechanism and likely oxocarbenium-ion-like transition states therein are supported by the powerful inhibition of the lytic transglycosylases by the natural inhibitor bulgecin (Figure 5.43b) and the suggestive disposition of its amide in the complex with a GH 23 enzyme. 

All of the three mentioned mechanisms involve oxocarbenium ion-like transition states and a pair of carboxylic acids at the active site however, they differ in several aspects. The inverting mechanism is a one-step reaction that results in the formation of a product with inverted stereochemistry at the anomeric center. The other two alternatives are retaining in stereochemistry at the anomeric center and differ from each other primarily in the nature of the intermediate in the second mechanism, this species is a covalent enzyme adduct, whereas in the third case it is believed to be a bicyclic oxazoline or oxazolinium ion. ... 

Matsson and Westaway. Until recently, there was debate about what determines the magnitude of a-secondary hydron KIEs. It has become clear that while there is an inverse contribution from the shortening of the CE-HE bond length in an oxocarbenium ion(-like) transition state, this contribution is similar in different transition states and the factor that determines the size of the KIE in a given reaction is the out-of-plane bending modes. These can vary from inverse to large and normal, depending on the TS structure. 

The experimental KIEs were qualitatively similar to other hydrolysis reactions. The primary leaving group 9- N KIE = 1.026 0.004 indicated extensive Cl -N9 bond breakage at the transition state. The a- and )8-secondary KIEs indicated an oxocarbenium ion-like transition state, F- H KIE = 1.150 0.006, 2 - H KIE = 1.161 0.003, while the primary carbon KIE was too large for a stepwise mechanism, F- C KIE = 1.044 0.004. The large remote 5-secondary H KIE, 5 - H KIE = 1.051 0.003, was interpreted as being due to an enzyme-induced conformation of the C5 hydroxymethyl group that can help stabilize the oxocarbenium ion-like AnDn transition state (see Section 3). 

Oxocarbenium ion stabilization. Even though all glycoside reactions appear to proceed through oxocarbenium ion(-like) transition states or intermediates, not all enzymes interact strongly with the sugar part of the substrate. This point will not easily be addressed solely with KIE studies, but it is an important issue in catalysis. 

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