The enzymatic introduction of a functional group into a biologically important molecule is not only specific with regard to the location at which the reaction occurs in the molecule (see Chapter 4, Problem 50), but also usually specific in the stereochemistry obtained. The biosynthesis of epinephrine first requires that a hydroxy group be introduced specifically to produce (-)-norepinephrine from the achiral substrate dopamine. (The completion of the synthesis of epinephrine will be presented in Problem 71 of Chapter 9.) Only the (-) enantiomer is functional in the appropriate physiological manner, so the synthesis must be highly stereoselective.

(a) Is the configuration of (-) norepinephrine R or S?
(b) In the absence of an enzyme, would the transition states of a radical oxidation leading to (-)- and (+)-norepinephrine be of equal or unequal energy? What term describes the relation between these transition states
(c) In your own words, describe how the enzyme must affect the energy of these transition states to favor production of the (-) enantiomer. Does the enzyme have to be chiral or can it be achiral?

Transcribed Image Text:

HO H HO но Dopamine B-monooxygenase, 02 CH2NH2 HO но Dopamine )-Norepinephrine