HCI_H3 Chem_H3 Prelims solutions 2008

Hwa Chong Institution H3 Pharmaceutical Chemistry 2008 Preliminary Examinations 2008 (Suggested Solutions) Question 1 (a)(i) Penicillins inhibit irreversibly the enzyme transpeptidase involved in the final stage of bacterial cell wall formation (a)(ii) R, R, S (a)(iii) Chemical hydrolysis will not selectively hydrolyse the acyclic amide only, but will also lead to the hydrolysis of the strained β-lactam ring in penicillin-G (a)(iv) NSOH2NHCO2HOCH3OCH3OClδ+δ− NSONHCO2HOCH3OCH3OHCl NSONHCO2HOCH3OCH3HO (a)(v) δ+δ−NSONHCO2HHOSerOHNSNHCO2HHOOSerOH NSNHCO2HHOOSerOHHNSNHCO2HHOOSerOδ+δ−OHH HNSNHCO2HHOSerOOOHHHNSNHCO2HHOSerOHOOHInactive as antibiotic (a)(vi) By increasing the steric bulk of the side chain as in methicillin, the approach of a β-lactamase enzyme to the β-lactam ring is hindered in the semi-synthetic methicillin, giving it more resistance to enzymic hydrolysis (b)(i) Sulphonamides behave as competitive inhibitors to the enzyme dihydropteroate synthetase, competing with the natural substrate 4-aminobenzoic acid and leads to the disruption of folic acid biosynthesis, which is vital for bacterial growth. (b)(ii) Chlorosulphonic acid is a very strong acid and protonates itself to give the electrophile, explaining why OH is the leaving group and why chlorosulphonation rather than sulphonation is the result.

SOHOOCl2SOOOCl+SOOOClHHSOOClElectrophile (b)(iii) SOOClNHCOCH3slowNHCOCH3 HSOOClSOOClO- ClSO2OHNHCOCH3 SOOClNNNH2 NHCOCH3 SOOClNNNHH NHCOCH3 SOONNNHH- Cl -- H +NHCOCH3 SOONHNN (c)(i) Any two: The amino functional group (-NH2) is essential for activity The amino and the sulphonyl group have to be para to each other, i.e. a para-disubstituted ring is essential. The anilo (Ph-NH2) amino group may be disubstituted, but optimum activity is observed with the unsubstituted form. Replacement of the central benzene ring (aromatic) or additional functional groups on the benzene ring diminishes activity. N-monosubstitution on SO2NH2 increases potency, especially with heteroaromatic groups. N-disubstitution on SO2NH2 leads to inactive compounds. (c)(ii) Prodrug – it is metabolised to sulphanilamide in the body, accounting for its in vivo activity

Question 2 (a) Stimulants (b) Caffeine Nicotine Competitive antagonist to adenosine receptors Agonist to acetylcholine receptors Works by increasing amount of adrenaline and noradrenaline Works by increasing amount