RJC_Chemistry H3 (Pharmaceutical Chem) with Ans

RAFFLES JUNIOR COLLEGE PRELIMINARY EXAMINATION 2008 HIGHER 3 PHARMACEUTICAL CHEMISTRY 9812/01 Paper 1 28 August 2008 2 hour 30 minutes Candidates answer on separate paper. Additional Materials: Answer Paper Data Booklet READ THESE INSTRUCTIONS FIRST DO NOT open this question booklet until you are told to do so. Write your name, civics tutorial group and index number in the spaces provided on the Cover Page and the writing papers. Write in dark blue or black pen on both sides of the writing papers. You may use a soft pencil for any diagrams, graphs or rough working. Do not use staples, paper clips, highlighters, glue or correction fluid. Answer any five questions. Begin each question on a fresh sheet of paper. A Data Booklet is provided. Do not write anything on it. You are reminded of the need for good Englis h and clear presentation in your answers. The number of marks is given in brackets [ ] at the end of each question or part question. At the end of the examination, fasten all your work securely together. This question booklet consists of 12 printed pages. © RJC 2008 [Turn over

2 1(a) Reserpine is a natural o ccurring drug that has been used for centuries in ancient India to treat hypertension, c holera and snakebites. It competes with neurotransmitters such as serotonin and dopamine for the storage vesicles in the pre–synaptic nerve. N H N O O OCH3 OR N H H2N HO reserpine serotonin (i) Based on the structure of serotonin as shown, copy out the structure of the reserpine molecule and circle t he most likely part(s) of reserpine that is responsible for its action. (ii) Suggest two physiological effects of t he neurotransmitters mentioned above. Two of the steps involved in the synthesis of reserpine are shown below. O OH H H H H H O Step 1 Br2 X Step 2 NaOMe MeOH O H H H H H O O H OMe 2 1 (iii) Predict the structure for X. Show the mechanism involved in Step 1 and include the stereochemis try of the intermediate X. State also the configurations (R or S) of the two carbon centres (C–1 and C–2). (iv) Step 2 involves two reactions to give the desired product as shown above. What is / are the type of reaction(s) involved? (v) Name the side reaction that might occur in Step 2. [10] © RJC 2008

3 Pseudoreserpine is another nat ural product which is ex tracted from the roots of plants. Pseudoreserpine and rese rpine are shown below, and both molecules contain a chromophore that absorbs UV radiation. N H N O O OH OR N H N O O OCH3 OR pseudoreserpine reserpine (vi) Explain the term chromophore and draw the chromophore that is responsible for the UV absorption. (vii) Pseudoreserpine has λmax = 282 nm and molar absorptivity,