Passage
High blood pressure, or hypertension, is a prevalent condition in the United States. One in three adults has hypertension, and approximately 20% do not know that they have it. If left untreated, high blood pressure can lead to major health issues, including stroke, heart attack, and kidney disease or failure. A number of drugs can help control hypertension, including those shown in Table 1. These drugs can be classified into different groups based on their mechanism of action.Table 1 Drugs Used to Treat High Blood Pressure
Labetalol (Figure 1) exists as four stereoisomers and is administered as a mixture of all four. This drug can be classified as a pseudohybrid drug because two of the isomers, (R,R) and (S,R) , exhibit biological activity; the other two isomers, (S,S) and (R,S) , are not active. The (R,R) isomer acts as a nonselective β-adrenergic receptor blocker, and the (S,R) isomer acts as a selective α-adrenergic receptor blocker.
Figure 1 Structure of (±) -labetalol and l-epinephrinel-epinephrine (Figure 1) is the agonist of the α- and β-adrenergic receptors. The structural motifs that allow l-epinephrine to bind to the adrenergic receptors include an amine separated from an aromatic ring by two carbon units, a hydroxyl group at a chiral center beta to the amine, and two hydroxyl groups on the aromatic ring in the meta and para positions. With a few structural modifications, the agonist l-epinephrine can be converted into the antagonist labetalol. Substitution of a hydroxyl on the aromatic ring with an amide group and extension of the methyl group on the amine transforms l-epinephrine into labetalol. These substitutions keep a majority of the structural motifs necessary for labetalol to mimic l-epinephrine and bind to the adrenergic receptors.
- What position(s) on the analog of labetalol would be considered stereocenters?

Question

Passage
High blood pressure, or hypertension, is a prevalent condition in the United States. One in three adults has hypertension, and approximately 20% do not know that they have it. If left untreated, high blood pressure can lead to major health issues, including stroke, heart attack, and kidney disease or failure. A number of drugs can help control hypertension, including those shown in Table 1. These drugs can be classified into different groups based on their mechanism of action.Table 1 Drugs Used to Treat High Blood Pressure

Labetalol (Figure 1) exists as four stereoisomers and is administered as a mixture of all four. This drug can be classified as a pseudohybrid drug because two of the isomers, (R,R) and (S,R) , exhibit biological activity; the other two isomers, (S,S) and (R,S) , are not active. The (R,R) isomer acts as a nonselective β-adrenergic receptor blocker, and the (S,R) isomer acts as a selective α-adrenergic receptor blocker.

Figure 1 Structure of (±) -labetalol and l-epinephrinel-epinephrine (Figure 1) is the agonist of the α- and β-adrenergic receptors. The structural motifs that allow l-epinephrine to bind to the adrenergic receptors include an amine separated from an aromatic ring by two carbon units, a hydroxyl group at a chiral center beta to the amine, and two hydroxyl groups on the aromatic ring in the meta and para positions. With a few structural modifications, the agonist l-epinephrine can be converted into the antagonist labetalol. Substitution of a hydroxyl on the aromatic ring with an amide group and extension of the methyl group on the amine transforms l-epinephrine into labetalol. These substitutions keep a majority of the structural motifs necessary for labetalol to mimic l-epinephrine and bind to the adrenergic receptors.
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What position(s) on the analog of labetalol would be considered stereocenters?

Quizplus · Accepted Answer

11ecba2d_125a_86f2_a3bf_eb832e52ea99_MD0008_00 A stereocenter is an atom that when two substituents switch positions, a stereoisomer is formed. A carbon that is sp³ hybridized and is attached to four different groups is called a chiral center. If the central carbon is bonded to two or more identical atoms, then subsequent atoms should be compared to determine whether the groups are truly identical. This process should be repeated until a difference is found or the chains end. If no difference is found, then the four groups to which the carbon is attached are not all different and the central carbon is not a stereocenter. The carbon at position 3 is bonded to two other carbons, one bonded to oxygen and one bonded to nitrogen. Therefore, the two groups are different. In all, position 3 is attached to: * -CH₂O- *-OH * H * -CH₂N- The central carbon at this position is bonded to four different groups, and is therefore a stereocenter. (Choices A and B) Positions 1 and 2 each contain only three attachments. The central carbon in both positions is sp² hybridized because there is a double bond to each, and atoms that are sp² hybridized are stereocenters only if a stereoisomer is formed when two substituents are switched. (Choice D) Both positions 3 and 4 contain four attachments each, and position 3 contains four unique attachments. However, position 4 contains only three unique attachments because two of the four are to hydrogen atoms. Educational objective: A stereocenter is any atom that when two substituents switch positions, a stereoisomer is formed. A chiral center is an atom with four unique attachments. If a central atom is bonded to two or more identical atoms, the next atom in each chain should be considered to determine if the attachments are the same or different.

Passage High Blood Pressure, or Hypertension, Is a Prevalent Condition in in the United