Page 1 of 17 Office Use Only Semester Two (November) 2014 Examination Period Faculty of Pharmacy and Pharmaceutical Sciences UNIT CODE: PSC1022 TITLE OF PAPER: Bioorganic and Medicinal Chemistry II EXAM DURATION: 3 hours writing time READING TIME: 10 minutes THIS PAPER IS FOR STUDENTS STUDYING AT:  Berwick  Clayton  Malaysia  Off Campus Learning  Open Learning  Caulfield  Gippsland  Peninsula  Enhancement Studies  Sth Africa  Parkville  Other (specify) During an exam, you must not have in your possession, a book, notes, paper, electronic device/s, calculator, pencil case, mobile phone or other material/item which has not been authorised for the exam or specifically permitted as noted below. Any material or item on your desk, chair or person will be deemed to be in your possession. You are reminded that possession of unauthorised materials, or attempting to cheat or cheating in an exam is a discipline offence under Part 7 of the Monash University (Council) Regulations. No exam paper or other exam materials are to be removed from the room. AUTHORISED MATERIALS OPEN BOOK  YES  NO CALCULATORS  YES  NO If ‘YES’ has been selected, only scientific calculators with a "Monash University, Faculty of Pharmacy and Pharmaceutical Sciences Approved" sticker attached are permitted in examinations for Pharmacy and Pharmaceutical Science students. No graphic calculators will be permitted. SPECIFICALLY PERMITTED ITEMS  YES  NO if yes, items permitted are: Candidates must complete this section if required to write answers within this paper STUDENT ID: __ __ __ __ __ __ __ __ DESK NUMBER: __ __ __ __ __ Section A [60 marks] + Section B [96 marks] = 156 marks Section A Multiple Choice Questions [30 questions  2 = 60 marks] RECORD YOUR ANSWERS TO THESE QUESTIONS ON THE SEPARATE MULTIPLE CHOICE ANSWER SHEET PROVIDED. 1. Ligands such as ethylenediamine are referred to as: A bidentate B bidenated C tridentate D bidensate 2. The correct name for [CoCl(NH3)5]SO4 is: A chloridopentaamminecobalt(III) sulfate B pentaamminechloridocobalt(III) sulfate C chloridopentaamminecobalt(II) sulfate D pentaamminechloridocobalt(II) sulfate 3. Chlorpromazine is an anti-psychotic agent. What is the classification of the amines I and II? A I: primary aliphatic; II: primary aromatic B I: tertiary aliphatic, II: primary aromatic C I: tertiary aliphatic, II: tertiary aromatic D I: tertiary aromatic, II: tertiary aliphatic Page 2 of 17 4. Rank the following from most basic to least basic: A II, III, I, IV B IV, III, II, I C I, III, IV, II D III, IV, I, II 5. Which is the correct structure for diphenylamine? A I B II C III D IV 6. Many nucleophilic addition reactions of aldehydes and ketones are accelerated by acid or base. Acids catalyse these reactions by: A shifting the equilibrium of the reaction B making the carbonyl group less electrophilic C reacting with base produced during the reaction D making the carbonyl group more electrophilic E activating the nucleophile Page 3 of 17 Page 4 of 17 7. Arrange the compounds in order of increasing boiling point (lowest first). A III, I, IV, II B I, II, IV, III C III, IV, I, II D II, I, III, IV E None of the above 8. Which is the main product from the reaction of (S)-2-methylpentanal with an aqueous base? A I B II C III D IV 9. Which compound reacts with aqueous acid to give an aldehyde? A a B b C c D d 10. Which of the following is a characteristic reaction of carboxylic acids and their derivatives? A acetalisation B nucleophilic acyl substitution C nucleophilic acyl addition D electrophilic substitution 11. What is the IUPAC name for the following compound? A 2-oxohexanoic acid B 5-oxohexanoic acid C methyl butyroxo ketone D 5-ketohexanoic acid 12. Which compound is prepared by reaction of benzoic acid with ammonia and water? A a B b C c D d 13. Arrange the compounds in order of increasing acidity (lowest first). A IV, I, II, III B III, II, IV, I C IV, II, I, III D II, I, III, IV E None of the above Page 5 of 17 14. Which is the correct structure for phenyl benzoate? A a B b C c D d 15. Which is the product of the reaction of phthalic anhydride with methanol? A a B b C c D d E None of the above Page 6 of 17 16. Which is the final product of a series of reactions starting with ethyl benzoate and reacting with 1) aqueous sulfuric acid and heat, 2) thionyl chloride, and 3) ethylamine? A a B b C c D d 17. Which physical property of triacylglycerols rich in unsaturated fatty acids is responsible for the lower melting point than the corresponding saturated compounds? A hydrophobic attractions B hydrophilic interactions C cis-carbon-carbon double bond steric interactions D hydrogen bonding E increased interactions with water 18. Which reagents could be used to harden an oil to a fat? A NaBH4 / H2O B Ni / H2 C Ag(NH3)2 + / H2O D Cu2+ / buffer E heat 19. How many stereocentres are present in methandrostenolone (below)? A 4 B 5 C 6 D 8 Page 7 of 17 20. Phospholipids are an abundant class of natural lipids and make up about 40-50% of cell membranes. A phospholipid is derived from phosphatidic acid by esterification of the phosphate group with an alcohol. Which of the following is NOT one of the most common alcohols found in phospholipids? A choline B cholesterol C inositol D ethanolamine 21. Which polymers are correctly matched to their primary use? I) Kevlar and containers II) Polymethylmethacrylate and Plexiglas III) Polytetrafluoroethylene and non-stick coatings IV) PET and bulletproof vests A I, III B II, III C II, IV D III, IV 22. Which classification best describes the mechanism of the synthesis of polyamides via step growth polymerization? A nucleophilic acyl addition B nucleophilic acyl substitution C electrophilic addition D radical substitution 23. What kind of bonds connect nucleotides within a strand of DNA? A glycosidic bonds B hydrogen bonds C peptide bonds D phosphodiester bonds Page 8 of 17 24. What is the relationship between the following compounds? A enantiomers B anomers C meso compounds D diastereomers 25. Assign the stereocentres in D-Galactose according to the S/R-system. A 2R, 3R, 4R, 5R B 2R, 3R, 4S, 5S C 2R, 3S, 4S, 5R D 2S, 3S, 4R, 5R 26. What will reduction of D-fructose (below) with NaBH4 yield? A a single chiral alditol B two diastereomers C a pair of enantiomeric alditols D a meso compound Page 9 of 17 27. Which is the DNA complement for 5’-ACCGTTAAT-3’? A 5’-ATTAACGGT-3’ B 5’-GTTACCGGC-3’ C 5’-TGGCAATTA-3’ D 5’-CAATGGCCG-3’ 28. Which is the order of increasing percentage in cells of messenger RNA, transfer RNA, ribosomal RNA (least first)? A mRNA, tRNA, rRNA B tRNA, rRNA, mRNA C rRNA, tRNA, mRNA D mRNA, rRNA, tRNA 29. Which sequence of one-letter codes correctly represents the following hexapeptide? A TSYLMT B TSYKMT C TMLYST D TMKYST E TSFKMT 30. Which is the structure of the pentapeptide that gave lys-leu-phe on reaction with cyanogen bromide, and gave fragments met-lys, leu-phe, and arg on reaction with trypsin? A arg-met-phen-leu-lys B lys-leu-phe-arg-met C arg-met-lys-leu-phe D met-arg-lys-leu-phe EXAMINATION CONTINUES OVER PAGE Page 10 of 17 Section B Written Answer Questions [96 marks] ANSWER QUESTIONS ONE TO TEN IN THE BOOKLET PROVIDED. START EACH QUESTION ON A NEW PAGE. QUESTION ONE The amine shown below can be prepared from benzyl bromide. (a) Give reaction(s), mechanism(s) and reagents that would allow you to complete this transformation in good yield. (b) What is the IUPAC name for this amine? [6 + 1 = 7 marks] QUESTION TWO Predict the magnetic properties of the [Fe(CN)6] 3– complex anion. Justify your answer. Data: Fe3+ is a d5 ion; CN– is a strong-field ligand. [5 marks] Page 11 of 17 QUESTION THREE Metals interactions with Aβ peptide in amyloid plaques are associated with Alzheimer’s disease (AD) [“Alzheimer’s disease & metals: therapeutic opportunities”, V. B. Kenche and K. J. Barnham, British Journal of Pharmacology 2011, 163, 211-219]. Compounds, which prevent these interactions, may have potential as disease modifying strategies for treating AD. Clioquinol (shown below) has moderate affinity for metal ions and has been tested in clinical trials against AD. (a) Name the donor atoms in the functional groups, which enable this molecule to bind to transition metal ions. (b) What is the term used to describe the action of this compound when it forms a coordination complex? (c) Draw and classify two isomeric forms of the complex which could be formed between two of these organic molecules and a copper (II) ion. [2 + 2 + 6 = 10 marks] QUESTION FOUR Consider the following chemical transformations. a) Draw structures of products (1), (2), and (3). b) Give the IUPAC name for compound (1). c) Reaction of (1) gives product (2). Describe type of this reaction on the basis of the chemical transformation involved and the reaction mechanism. d) Name functional groups in compound (3). [6 + 1 + 2 + 2 = 11 marks] Page 12 of 17 QUESTION FIVE Consider the following chemical transformations. 1) Draw structures of products (1), (2), (3), and (5). 2) What is reagent (4)? 3) Give the IUPAC name for compound (1). 4) Name the functional group(s) in compound (2). [8 + 2 + 1 + 1 = 12 marks] QUESTION SIX (a) Show with chemical equations how soaps can be made from triglycerides. (b) Why is hard water problematic for triglyceride derived soaps? (c) Would you expect the following fatty acids to occur naturally? Explain your answer for each in 1-2 sentences. [2 + 1 + 4 = 7 marks] Page 13 of 17 QUESTION SEVEN Given the following structure, determine the polymer’s repeating unit; redraw the structure using simplified parenthetical notation, and name the polymer. [4 marks] QUESTION EIGHT (a) The chair conformation of β-D-glucopyranose is unusual in that all the substituents are equatorial. Draw the chair conformations of both α- and β-D-glucopyranose and their corresponding Haworth projections, ensuring that you label each diagram. (b) Draw the Fischer projection for the compound resulting from treatment of L-glucose with silver nitrate, and name the compound. [6 + 4 = 10 marks] Page 14 of 17 QUESTION NINE Given the structures of the deoxynucleotides below, redraw these structures to indicate the arrangement of the Watson-Crick base pairs between them. [6 marks] Page 15 of 17 QUESTION TEN Part A. The diagram below shows the binding mode of an analogue of the statin drug rosuvastatin into the active site of the enzyme HMG-CoA reductase. Seven important intermolecular interactions are shown numbered 1 through to 7. Also in the active site is a water molecule (labelled 8) which resides next to the ethyl side chain on the pyrimidine ring and is also adjacent to the side chain of leucine 562. Provide a descriptive name for each of the seven intermolecular interactions. Part B. Order the seven intermolecular interactions from weakest to strongest. [e.g. 6 < 3 and so forth]. Part C. For the interaction labelled 3 (aspartate, 690) suggest an alternative functional group to replace the alcohol group (OH) that would result in a stronger interaction. Name this new interaction. Page 16 of 17 Part D. For the water molecule labelled 8, which resides next to the ethyl side chain on the pyrimidine ring and leucine 562, suggest an alternative group to the ethyl group which could then displace the water molecule and allow the new group to further interact with the leucine 562 residue. Either name the group you intend to replace with the ethyl group or draw the structure in your exam booklet. Briefly explain the reasoning behind your choice. Explain the advantage of displacing the water molecule. [7 + 7 + 2 + 8 = 24 marks] END OF EXAMINATION Page 17 of 17