Oxazolinium ion intermediate

It is known that the hydrolysis reaction proceeds via an oxazolinium ion intermediate. Based on this Kobayashi and coworkers succeeded in designing a disaccharide oxazoline transition state analog self-condensing substrate to revert the native action of HAase towards synthesis of hyaluronan and derivatives thereof (see Figure 9.15). 

The proposed mechanism for enzymatic hydrolysis of hyaluronan involves nucleophilic attack of water at the anomeric carbon of the d-G1cNAc moiety via an oxazolinium ion intermediate (see Figure 9.16b). A water molecule can nucle-ophilically attack the oxazolinium anomeric carbon atom to open the oxazolinium ring, resulting in the formation of the hydrolysis products of a shortened HA molecule (see Figure 9.16c). 

At the catalytic domain of the HAase, there is a conserved DXE(D) motif stabilizing an oxazolinium-ion intermediate (or transition state), and hence the hydrolysis reaction mechanism is considered to be similar to that of chitinases. These observations are in accord with the concept of TSAS monomer, strongly suggesting that two EROPA reactions of Schemes 38 and 39 occur via an oxazolinium transition state. 

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. ... 

In the direct synthesis of (3-pyranosides starting from GlcNAc derivatives, oxazolinium ion 76 is assumed to be an intermediate, explaining the high (3-stereoselectivity. The glycosylation results with the less nucleophilic 4-OH acceptor 81 by oxazoline 2 compared to p-acetate 1 (entry 2, Table 4 vs. entry 2, Table 3, 13 vs. 20% yield) were, however, different suggesting another route to the glycoside. 

Af-methyl, AT-4-X-benzoyl) dipeptides (233 X = NO2, CN, CF3, Cl, Me) and of the corresponding A -acetyl compound (234). The proposed mechanism (Scheme 42) involves the formation of an intermediate oxazolinium ion (235), and is supported by a value of /o = -1.34. Although not mentioned by the authors, the lability of the peptide linkage in these compoimds may be due to the well-known gem-dimethyl effect. 

On the other hand, much information on the hydrolysis mechanism of chitin in vivo by a chitinase enzyme has accumulated, particularly since 1995. There are mainly two mechanistic aspects in terms of the nature of the reaction intermediate (1) an oxazolinium intermediate [64-67] and (2) an oxocarbenium ion intermediate or a covalent glycosyl carboxylate intermediate (Scheme 21) [68]. An X-ray crystallographic analysis of chitinase A was performed that suggested an oxazolinium intermediate (Fig. 11) [65]. 

The polymerization mechanism of the SIP and DIP is explained as follows In the initiation, N-alkylated oxazolinium salt is first formed. With the sulfonate initiator, the propagation via the oxazolinium species occurs to induce the SIP process, as the nucleophilicity of the counteranion is weak. When the counteranion of the salt is sufficiently nucleophilic as in the case of halides (X = Br, Cl), it catalyzes the rearrangement of the oxazolinium ion to 3-methyl-l-azonia-3-azaspiro[4.4] nonan-2-one salt, a spiro-structure, via a covalent-type alkyl halide species as an intermediate. This isomerization to form the spiro-intermediate is the key step of the DIP. Its formation is preferred since it is more thermodynamically stable than the oxazolinium ion, due to the more stable C=0 bond than the C=N bond (Scheme 12). This spiro salt is sufficiently electrophilic to suffer the attack of the counteranion or the monomer. The attack of the counteranion exclusively occurs at the pyrro-lidinium ring, and a covalent ethyleneurea species is generated selectively. ... 

With methyl p-toluenesulphonate all polymerisations proceed via ionic intermediates (oxazolinium or oxazinium ions), initiation and propagation being formulated as follows e.g. ... 

Acyloxonium ions (Section 7.3) are stabilized by heavy anions. The formation of acyloxonium ions is also assumed, this time as non-isolated intermediates, in the solvolysis of some tosylates. In reaction (7,12) with sodium acetate, the introduction of an acetyl group at position 6 and migration of benzoate to position 5 testify to the presence of a benzoxonium intermediate. Likewise, solvolysis of sulfonates presenting a frani -vicinal acetamido group involves an oxazolinium cation 7.28, the analogue of an acyloxonium. 

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