HCI_H3 Chem Prelim

HWA CHONG INSTITUTION C2 PRELIMINARY EXAMINATION CHEMISTRY 9812 Higher 3: Pharmaceutical Chemistry 18 September 2008 2 h 30 min Do not open this booklet until you are told to do so. INSTRUCTIONS TO CANDIDATES 1) This paper consists of 12 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 all the work you hand in. 3) Begin each question on a FRESH sheet of writing paper. A nil return is necessary for any unattempted question. 4) 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. This question booklet consists of 12 printed pages

Antibacterials are aimed at either killing bacteria (bacteriocidal) or inhibiting them from multiplying (bacteriostatic). One type of antibacterial drugs is the penicillins, which have revolutionized the history of modern medicine by their effectiveness against several pathogenic bacterial species that cause various forms of infections. 1 Penicillin G, the parent of all these antibiotics, was first isolated from a fungal species, Penicillium notatum. Since the discovery of this antibiotic, several modifications have been introduced to the parent structure. The discovery of 6-amino penici llamic acid (6-APA) in fermentation products constituted a major breakthrough in semisynthetic penicillin synthesis. The reaction scheme for the formation of methicillin is shown below: N O H O N S H CO2H O O N O H O N S H CO2H O N S H CO2H H2N Step StepII I CH3 CH3 penicillin G 6-APA methicillin (a) (i) penicillin G 6-APA methicillin Describe the mode of action of penicillins. [2] (ii) Assign the R/S configuration for the asymmetric carbons found in penicillin G. [2] (iii) Suggest why chemical hydrolysis in step I to form 6-APA is not appropriate. [1] (iv) Give the reagent in step II and outline the mechanism for the formation of methicillin. [2] (v) Many bacteria have developed resistance to drugs by producing enzymes ( β-lactamases) capable of hydrolyzing the β-lactam ring. Describe the β-lactamase mediated β-lactam ring hydrolysis, starting with penicillin G. You may assume that the reactive species in a β- lactamase enzyme is the hydroxyl group of a serine residue in the protein. (vi) Suggest why methicillin shows improved resistance to β-lactamase mediated β-lactam ring hydrolysis.