Aldehyde-induced ATPase activities

The Mechanism of Aldehyde-Induced ATPase Activities of Kinases... 

While checking a sample of 2,5-anhydromannose-6-P for fructose-6-P by incubating it with phosphofructokinase and MgATP, we discovered that this aldehyde, which is sterically hindered from forming an internal hemiacetal, induced an ATPase activity (6). Since aldehyde hydration shows a large inverse equilibrium isotope effect of 0.73 when the hydrogen on the carbonyl carbon is replaced by deuterium (7,8), 2,5-anhydroman-nose-6-P-l-d will be 60% hydrated, compared to 52% hydration of the unlabeled aldehyde. If the free aldehyde were the activator, 48% of the unlabeled and 40% of the deuterated compound would be active, and a normal deuterium isotope effect of 0.48/0.40 = 1.2 would be seen on V/K (the apparent first order rate constant) for the activator, while if the hydrate were the active form, an inverse isotope effect of 0.52/0.60 = 0.87 would be seen. The observed value of 1.23 0.03 showed that the free aldehyde and not the hydrate was the activator (6). 

Kitching and co-workers " " developed total syntheses of plakortones C, D, E, and F. Acquisition of plakortone D, the most effective activator of SR-Ca " -pumping ATPase, used stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 67 (Scheme 15.18). A derived lactone aldehyde was then coupled with an independently generated, sulfone activated side chain unit 68. The 5,6- -double bond, carried through the sequence as a protected, stereodefined diol, was released there by stereospecific sy/j-elimination via an orthoester derivative. Racemic plakortone E was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 69 was assembled first. 

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