HCI_H3_CHEM_P1

This document consists of 15 printed pages and 1 blank page. HWA CHONG INSTITUTION JC2 Preliminary Examinations Higher 3 CANDIDATE NAME CT GROUP 10S CENTRE NUMBER INDEX NUMBER PHARMACEUTICAL CHEMISTRY Paper 1 9812/01 21 September 2011 2 hours 30 minutes INSTRUCTIONS TO CANDIDATES 1) This paper consists of 15 printed pages (including this page). You should have a Data Booklet, a cover page and a set of writing papers. 2) Answer any five questions. 3) Write your name and CT clearly on the cover page and on all the work you hand in. 4) Begin each question on a FRESH sheet of writing paper. A nil return is necessary for any unattempted question. 5) At the end of the examination, fasten your cover page securely together with your answer scripts. INFORMATION FOR CANDIDATES The number of marks is given in brackets [ ] at the end of each question or part question. A Data Booklet is provided. You may use a calculator. You are reminded of the need for good English and clear presentation in your answers.

2 © Hwa Chong Institution 2011 9812 / 01 / JC2 Prelim 2011 1 (a) Penicillin belongs to a big family of -lactam antibiotics which inhibits bacterial cell wall biosynthesis by inhibiting glycopeptides transpe ptidase. The latter is an important enzyme in the synthesis of peptidoglycan. (i) Describe two modes of actions of antibacterial drugs other than inhibitions of cell wall biosynthesis. [2] (ii) Bacterial resistance to antibiotics is a problem in the pharmaceutical industry and one possible mode of action by -lactamase can be represented as follow. N SR O OH O -lactamase HN SR O OH O OH penicillin penicilloic acid By representing -lactamase as R-OH, suggest a mechanism to the above reaction. [3] (iii) Penicillin works as an inhibitor because of the conformational similarity between the amide bond of the -lactam ring and the D-Ala-D-Ala termini in glycopeptides transpeptidase. Suggest why penicilloic acid is inactive in killing bacteria. [1] (iv) One approach that was taken to fight -lactamase was to develop potent inhibitors for -lactamase. The -lactamase inhibitor can be used in conjunction with penicillins to allow the antibiotic to destroy bacterial cell without being affected by the -lactamase. An example of a -lactamase inhibitor is sulbactam and its reaction with -lactamase is shown below. N S O OH O O O R-OH + R O O HN CO2H SO2H sulbactam Is sulbactam a reversible or an irreversible inhibitor? Explain briefly. [2]

3 © Hwa Chong Institution 2011 9812 / 01 / JC2 Prelim 2011 (b) Novobiocin is a coumarmycin-family antibiotics and it inhibits the function of DNA gyrase. O OR OHH3CO OCONH2 novobiocin O OH O N H O where R = Draw two possible chair conformations of novobi ocin, indicating the more stable confo