Exam 6: Organic Chemistry

Passage The β-lactam scaffold is an important feature in a class of broad-spectrum antibiotics that includes the penicillins, cephalosporins, and monobactams.  These antibiotics are used to treat a variety of diseases caused by bacteria.  The penicillins work by inhibiting a step in the synthesis of peptidoglycan.  However, the development of antibiotic resistance in the form of enzymes such as β-lactamase is an ongoing problem.An aromatic ring linked to the β-lactam ring has been reported to participate in hydrophobic interactions with β-lactamase active sites, and an aromatic ring bonded to the nitrogen of the β-lactam has shown to be beneficial to biological activity.  With this in mind, researchers synthesized a group of penicillanic acid analogues with substituted aromatic rings bonded to the β-lactam ring in an effort to overcome the challenge of antibiotic resistance.  The substituents on the aromatic rings were varied, including -OCH₃ and -NO₂, to make several analogues.  A key step in the synthesis of these analogues was the coupling of Compounds 1 and 2 to form a compound with two β-lactam rings (Reaction 1). Reaction 1The researchers studied the analogues' structure-activity relationship and antimicrobial activity against the gram-negative bacteria Escherichia coli and the gram-positive bacteria Staphylococcus aureus.  Ampicillin, a penicillin derivative used to treat illnesses brought about by gram-positive and gram-negative bacteria, was used as a control.  The minimal inhibitory concentrations are shown in Table 1.Table 1  Minimal Inhibitory Concentration (MIC) The penicillanic acid analogues were tested for their effect on mammalian cell viability because toxicity to cells is also an important factor to consider for potential drug candidates.  The general acceptable level of cell viability for a drug candidate is 70%.  These results are shown in Figure 1. Figure 1  Cell viability assay results Adapted from De rosa M, Vigliotta G, Palma G, Saturnino C, Soriente A. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation. Molecules. 2015. -The key step in the synthesis of the penicillin analogues shown in Reaction 1 is the coupling of Compounds 1 and 2, driven by dicyclohexylcarbodiimide.  Which functional group forms in this reaction?

Passage A group of students studied the reactivity of four alkyl halides (R−X) in two nucleophilic substitution reactions.  Nucleophilic substitution reactions can go through one of two mechanisms.  The S_N2 reaction requires substitution of a leaving group with a nucleophile in a single step (Reaction 1), and the S_N1 reaction requires elimination of the leaving group and formation of an intermediate before nucleophilic substitution can occur, resulting in a two-step process (Reaction 2).R−X + NaI → R−I + NaX↓Reaction 1R−X + AgNO₃ → R⁺ + AgX↓ + HOCH₂CH₃ → R−OCH₂CH₃ + HNO₃Reaction 2Experiment 1The students performed the S_N2 reaction (Reaction 1) by the addition of a few drops of each alkyl halide into a separate test tube containing 1 mL of 15% solution of NaI in acetone at 25°C.  After mixing, they monitored the reaction for the formation of a precipitate (sodium halide salt).  If no precipitate formed after 5 minutes, they raised the temperature of the reaction to 50°C and again checked for the formation of a precipitate.  Formation of a precipitate indicated the substrate underwent nucleophilic substitution.  The results observed for the Finkelstein reaction are shown in Table 1.Table 1  Results of the S_N2 Reaction Experiment 2The students repeated the procedure followed in Experiment 1 except they added a few drops of each alkyl halide into a separate test tube containing 1 mL of 1% solution of AgNO₃ in ethanol at 25°C.  The results observed for this reaction are shown in Table 2.Table 2  Results of the S_N1 Reaction -Suppose that Experiment 1 was done in diethyl ether instead of acetone, and NaI was replaced with another nucleophile.  The conjugate base of which of the following compounds would be the most nucleophilic?

Passage The β-lactam scaffold is an important feature in a class of broad-spectrum antibiotics that includes the penicillins, cephalosporins, and monobactams.  These antibiotics are used to treat a variety of diseases caused by bacteria.  The penicillins work by inhibiting a step in the synthesis of peptidoglycan.  However, the development of antibiotic resistance in the form of enzymes such as β-lactamase is an ongoing problem.An aromatic ring linked to the β-lactam ring has been reported to participate in hydrophobic interactions with β-lactamase active sites, and an aromatic ring bonded to the nitrogen of the β-lactam has shown to be beneficial to biological activity.  With this in mind, researchers synthesized a group of penicillanic acid analogues with substituted aromatic rings bonded to the β-lactam ring in an effort to overcome the challenge of antibiotic resistance.  The substituents on the aromatic rings were varied, including -OCH₃ and -NO₂, to make several analogues.  A key step in the synthesis of these analogues was the coupling of Compounds 1 and 2 to form a compound with two β-lactam rings (Reaction 1). Reaction 1The researchers studied the analogues' structure-activity relationship and antimicrobial activity against the gram-negative bacteria Escherichia coli and the gram-positive bacteria Staphylococcus aureus.  Ampicillin, a penicillin derivative used to treat illnesses brought about by gram-positive and gram-negative bacteria, was used as a control.  The minimal inhibitory concentrations are shown in Table 1.Table 1  Minimal Inhibitory Concentration (MIC) The penicillanic acid analogues were tested for their effect on mammalian cell viability because toxicity to cells is also an important factor to consider for potential drug candidates.  The general acceptable level of cell viability for a drug candidate is 70%.  These results are shown in Figure 1. Figure 1  Cell viability assay results Adapted from De rosa M, Vigliotta G, Palma G, Saturnino C, Soriente A. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation. Molecules. 2015. -The preparation of Compound 1 begins with a carboxylic acid (CA) derivative undergoing nucleophilic acyl substitution with methanol under reflux conditions to form butanoic acid with a methyl ester substituent on carbon 4.  Which structure was most likely the starting CA derivative?

Passage Students perform a synthesis of a carboxylic acid derivative.They mix a 10.00-mL sample of hexanoic acid, 2.33 mL of ethanol, and 0.64 mL of concentrated sulfuric acid in a flask with a water condenser fitted to its neck.  The mixture is boiled for one hour and then poured into water when the reaction is complete.  The aqueous and organic layers are separated, and the organic layer is washed once with NaHCO₃ and twice with water.  Solid Na₂SO₄ is added to the organic layer to remove any water present.  The organic layer and Na₂SO₄ are separated by filtration.  The filtrate is purified by fractional distillation to yield the carboxylic acid derivative, a colorless liquid. -Which of the following reactions will convert hexanoic acid and the carboxylic acid derivative described in the passage to the same product?

The number of different stereoisomers that exist for the compound shown below is:

Passage Chloramphenicol (Compound 1) is an antibiotic that acts against gram-positive and gram-negative bacteria by blocking peptidyl transfer, which inhibits protein synthesis by bacterial ribosomes.  However, it tastes bitter, so most patients cannot tolerate it.  As a result, synthesis of hydroxyl-substituted chloramphenicol analogues has become of interest because ester chloramphenicol analogues taste better than chloramphenicol.  Substituents on the primary hydroxyl group of chloramphenicol analogues are typically hydrolyzed quickly in vivo to regenerate Compound 1.  Compound 3, a chloramphenicol analogue, was synthesized by the transesterification of Compound 1 and vinyl propionate (Compound 2), catalyzed by the enzyme Lip_BA lipase (Figure 1). Figure 1  Transesterification of chloramphenicol catalyzed by Lip_BAAlthough enzyme catalysis allows for efficient regiospecific and stereospecific bond formation, the reaction conditions for the conversion efficiency of Compound 1 to Compound 3, as well as the purity of Compound 3, must also be optimized.  The reaction solvent, temperature, and time were studied to find the conditions that gave the highest conversion rate and purity.  Each parameter was altered individually while all others were kept constant, and the enzyme concentration was 4.5 g/L in each trial.  The results of this study are shown in Table 1.  The purity of Compound 3 was found to be over 90% when 1,4-dioxane was used and over 70% when dichloromethane was used.Table 1  Transesterification Conditions Optimization The transesterification reaction was monitored by thin-layer chromatography (Figure 2), and the product was confirmed by ¹H NMR.  The ¹H NMR spectra of Compounds 1 and 3 can be distinguished by the shift of H_e and H_f due to the addition of the electronegative ester functional group. Figure 2  Thin-layer chromatography of reaction mixture Adapted from F. Dong et al., "Transesterification Synthesis of Chloramphenicol." Molecules. ©2017 MDPI. -Which of the following experimental conditions does NOT contribute to the highest conversion efficiency?

Passage Aldehydes are organic compounds encountered in everyday life and used as intermediates in metabolism.  Common aldehydes include formaldehyde, which is used in the fixation of tissues, and cinnamaldehyde, which provides the flavor and smell of cinnamon (Figure 1). Figure 1  Common aldehydesThe aldol condensation shown in Figure 2 is an important carbon-carbon bond-forming reaction that has many applications in the synthesis of bioactive molecules.  It also takes place in some metabolic processes, such as the citric acid cycle and gluconeogenesis.  The aldol condensation begins with the aldol reaction, which can be acid- or base-catalyzed and requires nucleophilic addition to a carbonyl to provide the aldol product, which can be a β-hydroxy ketone or aldehyde.  The final step of the aldol condensation consists of an acid- or base-catalyzed dehydration of the aldol product to yield an α,β-unsaturated ketone or aldehyde. Figure 2  General aldol reaction and condensationThe reverse of an aldol reaction or condensation is known as a retro-aldol, which is important in metabolism, most notably in glycolysis.  This reaction breaks a carbon-carbon bond to form aldehydes and/or ketones.  In glycolysis, fructose 1,6-bisphosphate is broken down into an aldehyde and a ketone, glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP), respectively (Figure 3). Figure 3  Retro-aldol in glycolysis -Which of the following compounds would be a plausible intermediate in the base-catalyzed aldol reaction of the first step of the citric acid cycle shown below?

Passage The cryptophycins, isolated from cyanobacteria, are a family of macrocyclic molecules.  Researchers have studied the biological activity of these compounds and found that many of them are active against multi-drug-resistant tumor cells.Cryptophycin-52, an analogue of the natural cryptophycins, has been tested in clinical trials for its efficacy against cancer cells, but the studies were suspended due to neurotoxic side effects.  Nevertheless, the synthesis of similar analogues continues to be of interest in cancer research.  A key step in the synthesis of cryptophycin-52 is the stereospecific formation of an epoxide from an alkene and oxone (Figure 1), which can be facilitated by the Shi catalyst.  The Shi catalyst (Figure 2) is derived from the carbohydrate D-fructose and is known among organic chemists for its ability to form epoxides in hydrocarbons in a stereospecific manner. Figure 1  Shi epoxidation of compound 1 Figure 2  Structure of the Shi catalystThe epoxidation of compound 1 was monitored by thin-layer chromatography (TLC).  When the reaction was completed, high-performance liquid chromatography (HPLC) was used to analyze the epoxide product.  A chiral column that had an affinity for the desired epoxide was used.  A standard of the desired epoxide was obtained to optimize the conditions and determine the retention time of the epoxide.  The HPLC chromatogram of the epoxide standard is shown in Figure 3. Figure 3  HPLC of epoxide standard Adapted from Weiß C, Bogner T, Sammet B, Sewald N. Total synthesis and biological evaluation of fluorinated cryptophycins. Beilstein J Org Chem. 2012. -After isolation of compound 1, an infrared spectrum was obtained.  The spectrum gives all of the following information EXCEPT:

Passage Two key ingredients found in many soaps are PEG 150 distearate and ethylhexyl glycerin.  Both can be synthesized from glyceryl tristearate (Figure 1). Figure 1  Formation of PEG 150 distearate and ethylhexyl glycerin from glyceryl tristearateThe first step in this process requires the saponification of glyceryl tristearate.  The resulting stearate molecules can then react with PEG 150 in an acid-catalyzed Fischer esterification to form PEG 150 distearate.  The glycerol produced during saponification is used as a nucleophile to form ethylhexyl glycerin through a base-catalyzed S_N2 reaction with an ethylhexyl halide.Studies have shown that hand washing with soap can substantially reduce the number of germs present on hands and that washing hands before preparing food is particularly effective in reducing illness.  Researchers examined the effect of washing for 20 seconds with different amounts of soap containing PEG 150 distearate and ethylhexyl glycerin and found an inverse correlation between the volume of soap used and the amount of bacteria recovered from the hands.  The data are shown in Figure 2. Figure 2  Bacteria recovered from hands after washing with varying amounts of soapThe researchers then investigated the effect of hand washing with different kinds of soap on the transfer of bacteria from hands to objects.  Volunteers washed with a fixed volume of soap for 30 seconds, then handled sterilized plastic spheres for 30 seconds.  Bacteria were then recovered from the spheres.  The results are shown in Table 1.Table 1 Bacteria Recovered from Objects Adapted from  Fuls JL, Rodgers ND, Fischler GE, et al. Alternative hand contamination technique to compare the activities of antimicrobial and nonantimicrobial soaps under different test conditions. Appl Environ Microbiol. 2008. -Counting the number of bacteria recovered from which of the following would NOT help researchers verify that soap reduces the number of bacteria transferred to objects?

Passage Malaria is caused by the parasite Plasmodium falciparum and is transmitted through a female mosquito bite.  Although there are antimalarial treatments available, P. falciparum has become resistant to many of these drugs.  P. falciparum cells contain a respiratory organelle called the apicoplast that is necessary for the parasite's survival but is not found in humans.  Therefore, a new drug that targets this organelle could be useful in the treatment of malaria.A portion of the apicoplast protein ferredoxin (PfFd) is shown in Figure 1, with certain amino acid residues labeled.  In the apicoplast, ferredoxin NADP⁺ reductase (PfFNR) interacts electrostatically with PfFd and catalyzes an electron transfer reaction.  A compound that selectively inhibits this interaction could be a beneficial antimalarial agent. Figure 1  Structure of a portion of PfFdChalcone (Compound 3) is a compound that interacts with PfFd and exhibits antimalarial properties.  A series of chalcone derivatives (Compounds 4-8) were synthesized via the aldol condensation shown in Scheme 1, where nucleophilic addition of Compound 1 to Compound 2 is followed by elimination to yield α,β-unsaturated carbonyl molecules, Compounds 3-8. Scheme 1An inhibition assay was performed to compare chalcone (Compound 3) and its derivatives by determining the extent to which these compounds inhibited electron transfer between PfFNR and PfFd (Table 1).Table 1  Inhibition of electron transfer assay results Adapted from H. Suwito et al. "Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents." Molecules. ©2014 MDPI. -Based on the data in Table 1, what effect do the chalcone derivative substituents have on the percent inhibition relative to chalcone?

During the synthesis of a tosylate, which of the following pairs of atoms form a covalent bond?

A 100-mL aqueous HCl solution was made by diluting concentrated HCl 1:20 to 50 mL.  A portion of the resulting solution was then diluted 1:4 to make the final solution.  What was the volume of concentrated HCl that was diluted?

Passage A group of students studied the reactivity of four alkyl halides (R−X) in two nucleophilic substitution reactions.  Nucleophilic substitution reactions can go through one of two mechanisms.  The S_N2 reaction requires substitution of a leaving group with a nucleophile in a single step (Reaction 1), and the S_N1 reaction requires elimination of the leaving group and formation of an intermediate before nucleophilic substitution can occur, resulting in a two-step process (Reaction 2).R−X + NaI → R−I + NaX↓Reaction 1R−X + AgNO₃ → R⁺ + AgX↓ + HOCH₂CH₃ → R−OCH₂CH₃ + HNO₃Reaction 2Experiment 1The students performed the S_N2 reaction (Reaction 1) by the addition of a few drops of each alkyl halide into a separate test tube containing 1 mL of 15% solution of NaI in acetone at 25°C.  After mixing, they monitored the reaction for the formation of a precipitate (sodium halide salt).  If no precipitate formed after 5 minutes, they raised the temperature of the reaction to 50°C and again checked for the formation of a precipitate.  Formation of a precipitate indicated the substrate underwent nucleophilic substitution.  The results observed for the Finkelstein reaction are shown in Table 1.Table 1  Results of the S_N2 Reaction Experiment 2The students repeated the procedure followed in Experiment 1 except they added a few drops of each alkyl halide into a separate test tube containing 1 mL of 1% solution of AgNO₃ in ethanol at 25°C.  The results observed for this reaction are shown in Table 2.Table 2  Results of the S_N1 Reaction - Compounds 1 and 2 are both intermediates that could form by a reaction with AgNO₃ in ethanol, but Compound 1 is less stable than Compound 2 because:

The compound shown below has selected carbons labeled. Where are the two stereocenters, with one in the S configuration and the other in the R configuration, located?

Passage Chloramphenicol (Compound 1) is an antibiotic that acts against gram-positive and gram-negative bacteria by blocking peptidyl transfer, which inhibits protein synthesis by bacterial ribosomes.  However, it tastes bitter, so most patients cannot tolerate it.  As a result, synthesis of hydroxyl-substituted chloramphenicol analogues has become of interest because ester chloramphenicol analogues taste better than chloramphenicol.  Substituents on the primary hydroxyl group of chloramphenicol analogues are typically hydrolyzed quickly in vivo to regenerate Compound 1.  Compound 3, a chloramphenicol analogue, was synthesized by the transesterification of Compound 1 and vinyl propionate (Compound 2), catalyzed by the enzyme Lip_BA lipase (Figure 1). Figure 1  Transesterification of chloramphenicol catalyzed by Lip_BAAlthough enzyme catalysis allows for efficient regiospecific and stereospecific bond formation, the reaction conditions for the conversion efficiency of Compound 1 to Compound 3, as well as the purity of Compound 3, must also be optimized.  The reaction solvent, temperature, and time were studied to find the conditions that gave the highest conversion rate and purity.  Each parameter was altered individually while all others were kept constant, and the enzyme concentration was 4.5 g/L in each trial.  The results of this study are shown in Table 1.  The purity of Compound 3 was found to be over 90% when 1,4-dioxane was used and over 70% when dichloromethane was used.Table 1  Transesterification Conditions Optimization The transesterification reaction was monitored by thin-layer chromatography (Figure 2), and the product was confirmed by ¹H NMR.  The ¹H NMR spectra of Compounds 1 and 3 can be distinguished by the shift of H_e and H_f due to the addition of the electronegative ester functional group. Figure 2  Thin-layer chromatography of reaction mixture Adapted from F. Dong et al., "Transesterification Synthesis of Chloramphenicol." Molecules. ©2017 MDPI. -The major goal of synthesizing chloramphenicol analogues, such as Compound 3, was most likely:

Passage Ethanol is an important source of energy that is frequently used as a supplement to gasoline.  It can be obtained from renewable resources such as the cellulose found in plant matter.  When subjected to a process called gasification, the plant mass is converted to a mixture called syngas, composed predominantly of carbon monoxide and molecular hydrogen.  Syngas can be passed over a rhodium catalyst to generate ethanol and other products.  After using this method, a group of researchers analyzed the resulting products by gas chromatography using helium as a carrier gas.  The results are shown in Figure 1. Figure 1  Gas chromatograph of syngas catalysis productsMass spectrometry revealed that the process yielded similar amounts of ethanol, acetic acid, and acetaldehyde, with trace amounts of ethane.  In addition, the ethanol peak was found to be contaminated with ethyl acetate.  Another group of researchers in the same laboratory had recently produced Compound 1 as a by-product in a separate reaction.  They combined Compound 1 with purified ethyl acetate to form megestrol acetate, a drug used in the treatment of certain cancers.  This reaction also produced ethanol, as shown in Scheme 1. Scheme 1 Adapted from Lopez L, Velasco J, Montes V, Marinas A, Cabrera S, Boutonnet M, Järås S. Catalysts  2015. -During the conversion of Compound 2 to megestrol, why was the secondary alcohol affected, whereas the tertiary alcohol was not?

Passage Ethanol is an important source of energy that is frequently used as a supplement to gasoline.  It can be obtained from renewable resources such as the cellulose found in plant matter.  When subjected to a process called gasification, the plant mass is converted to a mixture called syngas, composed predominantly of carbon monoxide and molecular hydrogen.  Syngas can be passed over a rhodium catalyst to generate ethanol and other products.  After using this method, a group of researchers analyzed the resulting products by gas chromatography using helium as a carrier gas.  The results are shown in Figure 1. Figure 1  Gas chromatograph of syngas catalysis productsMass spectrometry revealed that the process yielded similar amounts of ethanol, acetic acid, and acetaldehyde, with trace amounts of ethane.  In addition, the ethanol peak was found to be contaminated with ethyl acetate.  Another group of researchers in the same laboratory had recently produced Compound 1 as a by-product in a separate reaction.  They combined Compound 1 with purified ethyl acetate to form megestrol acetate, a drug used in the treatment of certain cancers.  This reaction also produced ethanol, as shown in Scheme 1. Scheme 1 Adapted from Lopez L, Velasco J, Montes V, Marinas A, Cabrera S, Boutonnet M, Järås S. Catalysts  2015. -In Scheme 1, conversion of Compound 1 to Compound 2 most likely begins with which of the following steps?

Four alkyl halides: bromomethane, 2-bromobutane, 2-bromo-2-methylpropane, and 1-bromobutane, each react with water through solvolysis by an S_N1 reaction in which the solvent acts as the nucleophile.  In what order will these alkyl halides react to form alcohols, from fastest to slowest?

Passage Malaria is caused by the parasite Plasmodium falciparum and is transmitted through a female mosquito bite.  Although there are antimalarial treatments available, P. falciparum has become resistant to many of these drugs.  P. falciparum cells contain a respiratory organelle called the apicoplast that is necessary for the parasite's survival but is not found in humans.  Therefore, a new drug that targets this organelle could be useful in the treatment of malaria.A portion of the apicoplast protein ferredoxin (PfFd) is shown in Figure 1, with certain amino acid residues labeled.  In the apicoplast, ferredoxin NADP⁺ reductase (PfFNR) interacts electrostatically with PfFd and catalyzes an electron transfer reaction.  A compound that selectively inhibits this interaction could be a beneficial antimalarial agent. Figure 1  Structure of a portion of PfFdChalcone (Compound 3) is a compound that interacts with PfFd and exhibits antimalarial properties.  A series of chalcone derivatives (Compounds 4-8) were synthesized via the aldol condensation shown in Scheme 1, where nucleophilic addition of Compound 1 to Compound 2 is followed by elimination to yield α,β-unsaturated carbonyl molecules, Compounds 3-8. Scheme 1An inhibition assay was performed to compare chalcone (Compound 3) and its derivatives by determining the extent to which these compounds inhibited electron transfer between PfFNR and PfFd (Table 1).Table 1  Inhibition of electron transfer assay results Adapted from H. Suwito et al. "Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents." Molecules. ©2014 MDPI. -Which amino acid residue on PfFNR most likely interacts with the residues of PfFd shown in Figure 1?

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. -(S,R)- and (R,R)-labetalol, the active forms of the drug, can be described as which of the following?DiastereomersEnantiomersConformational isomers