Deficiency effects acrolein

Ketones and Aldehydes The R2C=0 and the RCH=0 carbon atoms absorb in a characteristic region. Acetone absorbs at 203.3 ppm, and acetaldehyde at 199.3 ppm. Alkyl substitution on the a-carbon causes a shift to the left of the C=0 absorption of 2-3 ppm until steric effects supervene. Replacement of the CH3 of acetone or acetaldehyde by a phenyl group causes a shift to the right of the C=0 absorption (acetophenone, 195.7 ppm benzaldehyde. 190.7 ppm) similarly, a,/3-unsaturation causes shifts to the right (acrolein, 192.1 ppm, compared with propionaldehyde, 201.5 ppm). Presumably, charge delocalization by the benzene ring or the double bond makes the carbonyl carbon less electron deficient. 

This approach has been applied to the delivery of the 5 -monophosphate of anticancer nucleoside, 2 -deoxy-5-fluorouridine (FdU) [78, 79], in which prodrug (59, R = 5 -FdU) cleaves to FdU 5 -monophosphate and acrolein in the presence of carboxyesterase. The prodrug inhibited DNA synthesis in both Chinese hamster ovary cells and thymidine kinase-deficient mouse fibroblasts this effect has been attributed to intracellular metabolism to FdU 5 -monophosphate and subsequent inhibition of thymidine monophosphate synthase. The prodrug was also as effective as 5-ffuorouracil in prolonging the life-span of mice with P-388 leukaemia. The prodrug was tolerated better by mice when administered with 2-mercaptoethanesulphonic acid, a scavenger for the toxic by-product, acrolein. 

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