The examination is comprised of ONE single part. You must answer FOUR of the SIX questions. Use a SEPARATE answer book for EACH question.

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1 UIVERSITY F EAST AGLIA School of Pharmacy Main Series UG Examination LIFE SCIECES CEMISTRY PA-4003Y Time allowed: 2 hours The examination is comprised of E single part. You must answer FUR of the SIX questions. Use a SEPARATE answer book for EAC question. The paper consists of 8 pages in total. The following will be provided: RA handout for Question 6. Dictionaries are not permitted in this examination. Do not take this question paper out of the examinations room. otes are not permitted in this examination. Do not turn over until you are told to do so by the Invigilator. (PA-4003Y) Module Contact: Dr Paul McDermott, PA Copyright of the University of East Anglia Version 2

2 2 1. Answer ALL parts (a) to. Procainamide is an anti-arrhythmic drug Procainamide 2 Starting materials (a) Provide a full retrosynthesis for procainamide to get back to the starting materials shown above. Briefly explain the strategy you have used. [30%] (b) Rank the three nitrogen atoms in procainamide in order of increasing basicity. Fully explain your answer with the aid of appropriate chemical diagrams. [30%] Suggest FUR peaks you would see in the IR spectrum for procainamide. For each peak state the wavenumber range in which you would expect to find the peak in the spectrum. [20%] Would you expect procainamide to have a longer λmax than 4-nitrobenzoic acid? Fully explain your answer. [20%] (PA-4003Y) Version 2

3 3 2. Answer ALL parts (a) to (h). Shown below are the structures of eight compounds from your top 25 drugs list (ote: some of the molecules A to may appear in more than one of the answers below). A B 2 Cl 2 C D E Cl F S 2 S G (a) Which TW compounds above contain more than one basic nitrogen? [8%] (b) Which TREE compounds above can exist as a zwitterion? [9%] Which E of the compounds above doesn t contain any -bond donor groups? [4%] Assign the configuration R or S to the chiral centre in compound G. Show all of your workings. [13%] (e) Which functional group in compound G corresponds to the softest nucleophile? Explain your answer. [15%] Question 2 continues... TUR VER (PA-4003Y) Version 2

4 4...question 2 continued. Shown below are 2 steps in the synthesis of compound F. Boc? Boc Cl? Boc step 1 step 2 I J K (f) Suggest reagents for steps 1 and 2. [5%] (g) Provide a full curly arrow mechanism for step 2. [20%] Compound D can be made via reaction of compound L with an organometallic reagent. (h) Suggest a structure for the organometallic reagent and provide a full curly arrow mechanism for this reaction. [26%] (PA-4003Y) Version 2

5 5 3. Answer ALL parts (a) to. Shown below are two different nucleophilic substitution reactions. When the concentration of nucleophile is doubled in reaction 1 the rate of reaction doubles. owever, when the concentration of nucleophile is doubled in reaction 2 the rate stays the same. Reaction 1 SPh 2 + SPh2 Reaction 2 SPh 2 Cl Cl + SPh 2 (a) Provide a full curly arrow mechanism for reaction 1. In your answer fully explain ALL of the features of this reaction that explain your choice of mechanism. [25%] (b) Provide a full curly arrow mechanism for reaction 2. In your answer fully explain ALL of the features of this reaction that explain your choice of mechanism. [25%] Shown below are the two energy profile diagrams for the substitution reactions. Match each of the energy profile diagrams to one of the two nucleophilic substitution reactions. In your answer draw the two energy profile diagrams and annotate them appropriately to fully explain your answer. [25%] Question 3 continues... TUR VER (PA-4003Y) Version 2

6 6...question 3 continued. For a third nucleophilic substitution reaction shown below suggest structure(s) for the reaction product(s). Fully explain your answer. [25%] (PA-4003Y) Version 2

7 7 4. Answer ALL parts (a) to. Pyridoxamine phosphate is a key intermediate in transamination reactions between amino acids and alpha-keto acids. 2 C 2 3 P 2 3 P 2 C C -Ketoglutarate Pyridoxamine phosphate (enzyme bound) 2 C A 2 C * 2 + B 2 C Glutamic acid (a) Provide a full curly arrow mechanism for the formation of imine A. [20%] (b) Draw structure B and provide a mechanism for its formation from A. [40%] Compound C is a natural metabolite found in the Staphylococcus aureus pathogen. When C is treated with aqueous hydrochloric acid a mixture of compounds D and E is obtained. Why is the amide bond in compound C only partially hydrolysed in this reaction? [10%] Draw a mechanism for the formation of compound D. Use your mechanism to explain the stereochemical outcome of this reaction. [30%] TUR VER (PA-4003Y) Version 2

8 8 5. Answer ALL parts (a) to (f). The reaction scheme below shows the pathway for lipogenesis. (a) Draw the structures for ALL of the compounds B, C and F. [30%] (b) What are the TW cofactors D and E that are involved in step (iv). [10%] Correctly label each of the FUR steps, (i) to (iv), as condensation, dehydration or hydrogenation reactions. [12%] Briefly describe FUR ways that an enzyme can help accelerate the rate of a reaction. [20%] (e) (f) Redraw the structure of compound A and highlight the most acidic hydrogen. Briefly explain your answer. [12%] Provide a full curly arrow mechanism for the tautomerisation of compound A into an enol form. [16%] (PA-4003Y) Version 2

9 9 6. Answer ALL parts (a) to (e). Shown on the handout for question 6 is a segment of RA. Write your student number on the handout. (a) n the handout, label the following: (i) 5 different functional groups (ii) 5 -end (iii) 3 -end (iv) Any anomeric carbon (v) Any Sugar (vi) Parts of the structure which would not be found in DA [20%] (b) You are interested in taking an IR spectrum of this fragment of RA. State the position of FUR main bands (and corresponding bonds) you would expect to see in the spectrum of this sample. [20%] In basic conditions, RA is unstable. Draw a curly arrow mechanism for the hydrolysis of RA. [20%] Explain why the shorter half-life of RA relative to DA is a key feature of this molecule s biological function. [20%] (e) Is DA UV active? Explain your answer. [20%] ED F PAPER (PA-4003Y) Version 2

2 Answer all the questions. 1 Alkenes and benzene both react with bromine but alkenes are much more reactive.

2 Answer all the questions. 1 Alkenes and benzene both react with bromine but alkenes are much more reactive. (a) Explain the relative resistance to bromination of benzene compared with alkenes. In your