Claisen rearrangements enzymatic

Claisen rearrangement, diosphenol-Claisen rearrangement, enzymatic Claisen... 

Chorismate Mutase catalyzed Claisen Rearrangement- 10 rate enhancement over non-enzymatic reaction... 

The differences in the rate constant for the water reaction and the catalyzed reactions reside in the mole fraction of substrate present as near attack conformers (NACs).171 These results and knowledge of the importance of transition-state stabilization in other cases support a proposal that enzymes utilize both NAC and transition-state stabilization in the mix required for the most efficient catalysis. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively.172 The fact that the reaction occurred faster in water than in methanol was attributed to greater stabilization of the TS in water by specific interactions with first-shell solvent molecules. The Claisen rearrangements of chorismate in water and at the active site of E. coli chorismate mutase have been compared.173 It follows that the efficiency of formation of NAC (7.8 kcal/mol) at the active site provides approximately 90% of the kinetic advantage of the enzymatic reaction as compared with the water reaction. 

The three-step procedure described for the preparation of the illustrated crotylsilanes is initiated with the hydrosilation of rac-3-butyn-2-ol. This procedure is significantly improved with respect to the positional selectivity of the hydrosilation resulting in exclusive formation of the racemic (E)-vinylsilane, and as a result the present procedure is much more amenable to scale-up than those previously described in the literature.8 The enzymatic resolution of the racemic secondary allylic alcohol (vinylsilane) has also been reported using commercially available lipase extracts. The use of a Johnson ortho ester Claisen rearrangement affords the (E)-crotylsilanes 4 in nearly enantiomerically pure form. 

The Claisen rearrangement, which displays a negative activation volume, is also accelerated in water. Thus, the non-enzymatic rearrangement of chorismate to pre-phenate occurs 100 times faster in water than in methanol [55]. The accelerating... 

Enzymatic studies with chorismate mutase prephenate dehydrogenase from Escherichia coli show that the chorismate prephenate analog 7 is not a substrate for chorismate mutase65. Both 7 and 8 are moderately competitive inhibitors for chorismate mutase. Ester derivatives 4 and 5, as well as 6, readily undergo Claisen rearrangements in organic solvents. 

Another new development in enzymatic reactions is the use of monoclonal antibodies as catalysts. These antibodies show regio- and stereoselectivity, substrate specificity, and rate acceleration. Hilvert12 has discussed three different reactions that are catalyzed by these antibodies decarboxylation, Dicls-Alder reactions, and Claisen rearrangements. This catalysis is a new field with tremendous possibilities. 

Despite various mechanistic investigations, it is still a matter of debate whether the enzymatic Claisen rearrangement proceeds through a concerted mechanism. See Y. Asano, J. J. Lee, T. L. Shieh, F. Spreafico, C. Kowal,... 

An attractive alternative synthesis was likewise developed by Firmenich. [105, 106] Pentylcyclopentenol, is enzymatically transesterified with dimethyl malo-nate, whereby the (S)-enantiomer remains unaltered, but this can be racemised in the presence of sulfuric acid. The malonate is converted into an allylsilylke-tene acetal, which is then subjected to a Claisen rearrangement this proceeds under the control of the aUyl alcohol at relatively low temperatures and with high stereoselectivity. After decarboxylation, there follows the key step in the synthesis a n-selective epoxidation with highly electrophilic peroxy-acids, such as peroxytrifluoroacetic acid. The high n-selectivity arises from electrostatic effects between the more electron-rich r-side of the douple bond and the partial... 

In bacteria, two soluble, multiactivity enzymes or enzyme complexes function in the utilization of chorismate for l-phenylalanine and L-tyrosine synthesis. A complex containing chorismate mutase and prephenate dehydratase activities has been observed. Although the reaction proceeds by what appears to be a Claisen rearrangement, the rate-limiting transition state appears to be different in the enzymatically controlled process. It is not known if formation of the higher-energy diaxial conformer (27) occurs after binding to the enzyme or is from an equilibrium mixture (Dewick, 1984 Floss, 1986 Jensen, 1986),... 

PROBLEM 20.45 We saw on page 1063 that chorismate undergoes a [3,3] sigmatropic shift (Claisen rearrangement) to prephenate catalyzed by the enzyme chorismate mutase. This enzyme-catalyzed reaction occurs more than 1 million times faster than the corresponding nonenzymatic reaction. How does the enzyme effect rate enhancement Both enzymatic and nonenzymatic reactions proceed through a chairlike transition state. However, the predominant conformer of chorismate in solution, as determined by H NMR spectroscopy, is the pseudodiequatorial conformer 2, which cannot undergo the reaction. 

Johnson, Gosteli, BeUus, and Enzymatic Claisen Rearrangements... 

Enzymatic Claisen rearrangement is observed in the rearrangement of chorismate 129 into prephenate 130 [89]. 

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

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