Higher 3 pharmaceutical chemistry concept test

Answer all three questions. Question 1 is worth 12 marks. Question 2 is worth 20

marks and question 3 is worth 18 marks.

Time: 1h 15mins

Question 2 diagrams http://faculty.smu.edu/jbuynak/Medicinal_Outline_11_9_04.pdf

Question 3 (i) to (iv) A level chemistryJ97 p4 phase equlibria Q7

Question 3 (v) 2nd part derived from A level chemistry J95 p2 Q6 (b) (ii)

Question 3 (vi) Adapted from VJC 09 Q 1(e)

50
 Acknowledgements

Question 1

Spectroscopy is a useful technique to determine the structure of unknown drugs.

One such technique is the use of infra-red (IR) spectroscopy. KBr is often used to
create discs for IR analysis. It is mixed with the compound of interest which is in solid
phase, forming a homogeneous mixture and then pressurised to form a small disc.

(a) Suggest why KBr is used and why it is suitable for that purpose. [1]

Other than KBr, Nujol (a type of oil) can also be used to create such discs. A lab
technician wants to analyse a compound that is known to be a hydrocarbon.

(b)However the IR spectrum obtained do not show any significant results. Why? [1]

N.B. x=1,2,3

(c) Does stretching a bond or bending a bond require more energy? [2]
(Hint: sp2 C-H stretch. ≈ 2900 cm-1: sp3 C-H stretch. ≈ 2700 cm-1)

(d) Suggest how can NMR distinguish between isomers. [1]

Write down:
i) four IR stretches one would expect from bupropion (shown above). [2]

ii) the M+: (M+1) : (M+2) ratio, round off to the nearest whole number. [1]

Draw the NMR spectrum, including the integral, multiplicity. [4]

Question 2

One of the drugs of “last resort” is Vancomycin is only used on patients after other
antibiotics failed. The structure of Vancomycin as well as NAG and NAM peptides,
found in peptidoglycan matrix of the cell wall of bacteria, are given below.

Terminal D-Ala-D-Ala of NAM-NAG peptides.

(a) From the structures and your knowledge, suggest how Vancomycin works-
including the bonds formed. [3]

(b) Using the diagram provided, draw a one-step mechanism in which

transpeptidase extends the the peptidoglycan chain. (There is no need to draw the
enzyme or the bilayer.) [1]

Explain if Gram-negative or Gram-positive bacteria is resistant to

Vancomycin. [1]
Hence name three examples other drugs of different classes that could affect
such bacteria. [1]

(c) (i) Suggest two reasons why Vancomycin is only administered as a “last
resort”. [1]

(ii) Briefly explain how vancomycin-resistant bacteria achieve the

resistance against vancomycin. [1]
(d) Darvon is a commonly used anesthetic as well as an analgesic.

Novrad is the enantiomer of Darvon. Draw it. [1]

Morphine is an opiate. Its structure is shown below.

What is a narcortic analgesic? [1]

Suggest if Darvon is an opoid analgesic. [2]

Darvon is administered using capsules – state one property darvon should

have for such administration. [1]

Darvon is administered in the salt form because it is less prone to abuse.

Suggest why. [1]
(d) MDMA is a hallucinogenic stimulant.

One synthetic pathway is shown below:

Suggest the intermediate formed from step I. [1]

(i) Name the reagents and conditions of step I to III [3].

(ii) Explain why it is better to use a tosyl intermediate to form MDMA rather than a
normal alkyl halide reaction. [1]

(iii) For the tosylation of alcohol, pyridine is used. Suggest a reason why. [1]
Question 3

Nucleosides are often used to make drugs with similar structures so that enzymes
would recognise the “wrongly” and thus unable to synthesis DNA or mRNA.

Explain the basis of UV/Visible spectroscopy and explain how you would conduct an
experiment to determine the concentration of guanosine (above) in a solution
mixture. [4]

HPLC is an important separation technique.

The column is packed with silica beads of 10 -6m which is smaller than usual. The
injected solute mixture can be separated in the column very sharply. High pressure
is applied to force the solvent through the column. Constant flow rate ensures
reproducibility. The flow rate is commonly 1.0 cm3min-1. A typical column is 20 cm
long and has a total volume of 2.50 cm3.

(i) What is one advantage of HPLC over conventional chromatography? [1]

(ii) What are 2 advantages of HPLC over TLC? [2]

(iii) Suggest why reproducibility is important in HPLC. [2]

(iv) Estimate how long the liquid stays in the column and how many silica beads are
used, assuming they are cubic? [3]

(v) Calculate the diameter of the column, in mm, explain its significance. [2]

(vi) 2 C-E is another hallucinogen which is tested to have greater potency than
MDMA. One modified structure is compound B.
 O
NH2

O 2 C-E

0.25g of pills found on a criminal is tested for compound B as followed:

I The amount of compound B in a tablet is analysed using HPLC.
The mixture contains 2.0 x 10-2 moldm-3 of MDMA (see question 2)
as internal standard.
50 cm3 of solvent buffered at pH 8.7 is used to dissolve the tablet
and the internal standard of MDMA.
Only two peaks are observed in the chromatogram obtained. The
ratio of peak areas of the substance which is eluted first to the one
which is eluted later is 3 : 5.

II The mass spectrum of compound B shows the following peaks in the

region of its molecular ion, which has m/e = 321.5.

Mass number Relative abundance (%)

320.5 50
III A
322.5 66.7
324.5 16.7

sample of compound B was heated with aqueous sodium

hydroxide for a few hours, followed by addition of dilute nitric acid.
Upon addition of aqueous silver nitrate solution, no precipitation
occurs.

Deduce the structure of compound B and the percentage purity of

the drug tablet.

[4]