Terminal epoxides such as 1 react with nucleophiles (H2O, Cl-, Br-, N3-, and CN-) at the primary oxirane carbon to give mostly anti-Markovnikov-type regioisomers 5a-d. The opening products of epoxide (R)-1 with chloride (5a), bromide (5b) and azide (5c) undergo enantio- and chemoselective oxidation by horse liver alcohol dehydrogenase and NAD+ to give the corresponding ketones 7a-c, and subsequently umbelliferone 4 by beta-elimination, leading to a fluorescence increase at landa em = 460 ± 20 nm (landa ex = 360 ± 20 nm). The epoxide hydrolysis products give no signal. This enantio- and chemo-selective fluorogenic assay for epoxide opening was used to search for catalytic antibodies for nucleophilic epoxide opening raised against 1,2-azidoammonium hapten 8 as a mimic for epoxide opening by azide and against chloromethyl phosphonate hapten 9 as a mimic for the transition state of chlorohydrin formation.
Fluorescence Assay and Screening of Epoxide Opening Reactions by Nucleophiles
CROTTI, PAOLO;
2004-01-01
Abstract
Terminal epoxides such as 1 react with nucleophiles (H2O, Cl-, Br-, N3-, and CN-) at the primary oxirane carbon to give mostly anti-Markovnikov-type regioisomers 5a-d. The opening products of epoxide (R)-1 with chloride (5a), bromide (5b) and azide (5c) undergo enantio- and chemoselective oxidation by horse liver alcohol dehydrogenase and NAD+ to give the corresponding ketones 7a-c, and subsequently umbelliferone 4 by beta-elimination, leading to a fluorescence increase at landa em = 460 ± 20 nm (landa ex = 360 ± 20 nm). The epoxide hydrolysis products give no signal. This enantio- and chemo-selective fluorogenic assay for epoxide opening was used to search for catalytic antibodies for nucleophilic epoxide opening raised against 1,2-azidoammonium hapten 8 as a mimic for epoxide opening by azide and against chloromethyl phosphonate hapten 9 as a mimic for the transition state of chlorohydrin formation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
