Deck 25: The Chemistry of Thioesters, Phosphate Esters, and Phosphate Anhydrides

Question 1

Draw a structure of S-isopropyl butanethioate.

Answer 1

A thioate indicates a thioester. Butanethioate indicates that the carbonyl is attached to a four-carbon chain. The S-isopropyl indicates an isopropyl group is attached directly to the sulfur. The structure is:

Question 2

Draw a structure of S-butyl cyclohexanecarbothioate.

Answer 2

A thioate indicates a thioester. A carbothiate indicates that the thioester is attached to a ring. The cyclohexane indicates a six-carbon ring. The S-butyl indicates a butyl group is attached directly to the sulfur. The structure is:

Question 3

Give the IUPAC and common name of the compound.

Answer 3

In systematic IUPAC naming, the thioester will have the parent name benzothioate, where the "thio" is inserted in the middle of "benzoate" to denote a thioester. A methyl group is attached directly to the sulfur, so the name will be S-methyl benzothioate.
In common naming, the thioesters will add the prefix -thio before the parent name and an S-prefix before the name of the alkyl group bonded to the sulfur. Thus, the common name is S-methyl thiobenzoate.

Question 4

What is the classification of the compound?

A) phosphate monoester
B) phosphate diester
C) phosphate triester
D) phosphoric acid

Question 5

Bisphosphoglycerate mutase catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate. Identify the phosphorus containing functional groups in 1,3-bisphosphoglycerate, then characterize each group as either a phosphate monoester, phosphate diester, phosphate anhydride, or pyrophosphate monoester.

Question 6

RNA can undergo spontaneous hydrolysis in basic solutions to form the cyclic compound below. Identify the phosphorus groups in both structures as either a phosphate monoester, phosphate diester, phosphate anhydride, or pyrophosphate monoester. Then propose a curved-arrow mechanism showing how the cyclic group can be formed.

Question 7

An acyl phosphate is an example of a mixed anhydride of a phosphoric and carboxylic acid. Draw the expected products of the acyl phosphate reacting with CH₃NH₂.

Question 8

Glutathione is a coenzyme consisting of the tripeptide Glu-Cys-Gly. The first step of the synthesis of glutathione is catalyzed by glutamyl cysteine synthetase, where glutamate reacts with ATP to form an acyl phosphate. In the second step, cysteine reacts with the acyl phosphate to form -Glu-Cys and phosphate ion. Note, the -Glu indicates the reaction occurs on the sidechain.
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Draw the acyl phosphate formed in the first step, and then draw a plausible curved-arrow mechanism showing how the acyl phosphate can be converted to -Glu-Cys.

Question 9

Aspartate reacts with ATP to give an unknown product and pyrophosphate. Draw the structure of the unknown product.

Question 10

Describe the expected splitting pattern for the phosphorus resonance in the structure.

Question 11

Given the phosphate diester, predict the splitting patterns for the hydrogens labeled a, b, and c. Assume the coupling constants for H-H and P-H splitting are the same.

Question 12

Predict the major organic product for the reaction. If there is no reaction, write NR and explain why.

Question 13

Give two reasons why thioesters (such as acetyl-CoA) are used in biological systems instead of their analogous oxygen esters.

Question 14

The reaction shown is part of the fatty acid synthesis pathway. ACP is an abbreviation for acyl carrier protein, and you do not need to know its structure. Identify the reagent that could perform this transformation.

A) NADPH
B) NADP⁺
C) LiAlH₄

Question 15

Predict the major organic product(s) for the reaction. If the reaction will not occur, write NR and explain why.

Question 16

Draw a plausible curved-arrow mechanism to show the base-catalyzed hydrolysis of the phosphate triester, then draw the hydrolysis products.

Question 17

DNA and RNA consist of phosphate diester backbone. With your knowledge of the reactivity of phosphate triesters and diesters towards hydrolysis, explain why a phosphate diester is an ideal functional group to connect monomer units in DNA and RNA.

Question 18

A phosphatase is

A) an enzyme that transfers a phosphate group to a molecule.
B) an enzyme that hydrolyses a phosphate group from a molecule.
C) an enzyme that reduces a phosphate group in a molecule.
D) an enzyme that oxidizes a phosphate group in a molecule.

Question 19

Predict the major organic products in the sequence:

Question 20

The structure of ATP is shown below. A nucleophile can react with which phosphorus atom?

A) the  phosphorus only
B) the  phosphorus only
C) the  phosphorus only
D) The , , and  phosphorus can all react with nucleophiles.

Question 21

DNA polymerase is an enzyme that catalyzes the nucleophilic attack of a 3ʹ-OH group of a deoxyribose sugar on the alpha-phosphorus of another nucleoside triphosphate. Draw a curved-arrow mechanism showing this attack, then identify the leaving group lost and what the driving force of the reaction is.

Question 22

Acetyl-CoA is formed from treating acetate ion with ATP and coenzyme A (CoASH). Explain the role of ATP in this reaction.

Question 23

Predict the major organic product for the reaction.

Question 24

Give two reasons why ATP is a high energy compound.

Question 25

Calculate the ΔG°´ for the phosphorylation of fructose-6-phosphate to fructose 1,6-biphosphate using ATP, given the following.