87116-21-0Relevant academic research and scientific papers
Pivalase catalytic antibodies: Towards abzymatic activation of prodrugs
Bensel, Nicolas,Reymond, Martine T.,Reymond, Jean-Louis
, p. 4604 - 4612 (2007/10/03)
Screening of monoclonal-an-tibody libraries generated against the tert-butyl phosphonate hapten 2 and the chloromethyl phosphonate hapten 3 with pivaloyloxymethyl-umbelliferone 1 as a fluorogenic substrate led to the isolation of eleven catalytic antibodies with rate accelerations around kcat/kuncat=103. The antibodies are not inhibited by the product and accept different acyloxymethyl derivatives of acidic phenols as substrates. The highest activity was found for the bulky, chemically less-reactive pivaloyloxymethyl group; there is no activity with acetoxymethyl or acetyl esters. This difference might reflect the preference of the immune system for hydrophobic interactions in binding and catalysis. Pivalase catalytic antibodies might be useful for activating orally available pivaloyloxymethyl prodrugs.
Reaction of (Acyloxy)alkyl α-Halides with Phenols: Effect of Nucleofugicity and Nucleophilicity on Product Distribution
Sloan, Kenneth B.,Koch, Suzanne A. M.
, p. 3777 - 3783 (2007/10/02)
The product distribution obtained from the reaction of (acyloxy)alkyl α-halides (1 or 5) with phenols was found to depend on the nucleophilicity of the phenol, the nucleofugicity of the leaving group, and the ability of the electrophile to stabilize a carbenium ion.More nucleophilic phenols tended to give more acylation while better leaving groups and more stable incipient carbenium ions in the electrophile tended to favor the formation of alkylated products.In addition, the reaction of methanol with 1a was found to give a mixture of acylated and alkylated products (40 : 60).Thus, a general trend for all the nucleophiles for which information is available suggests that better nucleophiles undergo relatively more acylation and that poorer nucleophiles undergo more alkylation.These results are suggested to be consistent with the observations of Westaway on the effect of leaving group nucleofugicity and nucleophilicity of the nucleophile on bond lengths in the SN2 transition state.Facile rearrangements of acylated to alkylated products and of one alkylated product to another caused by the phenolate anion were also observed in the 3-phenoxy-1(3H)-isobenzofuranone-phenyl 2-formylbenzoate series.
