1. Synthetic Strategies for 14 C Labelling of Drug Molecules Dr Sean L Kitson [email_address]

4. Introduction to 14 C

5. Discovery of 14 C Martin Kamen & Sam Ruben (27-FEB-1940) T 1/2 ~ 5730 Years

6. 14 C Starting Materials

7. Barium 14 C carbonate staircase

9. 14 C Synthetic Strategies 14 C labelling

11. 14 C Starting Material

12. Generation of ‘Dry’ 14 CO 2

13. Carboxylation

14. O -Methylation

16. S L Kitson, S J Jones et al . J Label Compd. Radiopharm 2010 , 53, 140-146

17. Key Step: A one pot construction of the quinolin-2-one ring under strong base

18. Aporphine skeleton ‘naturally occurring’ S L Kitson. J Label Compd Radiopharm; 2007 , 50, 290-294 S L Kitson. J Label Compd Radiopharm; 2006 , 49, 517-531

20. R etrosynthesis of Apomorphine

21. Synthesis of N- [carboxyl- 14 C]acetamide

22. Bischler-Napieralski Cyclodehydration

23. N -Methylation Reduction Step

24. Reduction-Pschorr Coupling

25. Chiral Separation

29. 14 C Synthetic route R T Brown et al . J Label Compd. Radiopharm 2009 , 52, 567-570

30. Target: [5- 14 C]Hex-5-ynoic acid [ 14 C]Acetylenes

31. [ 14 C]Acetylenes: Ohira Bestmann Reagent

32. 14 C Acetylene Synthesis Overall Radiochemical Yield 29 % from [ 14 C]KCN

33. [ 14 C]ZT-1: a new generation of acetylcholinesterase (AChE) inhibitors L Leman, S L Kitson et al. J. Label Compd. Radiopharm 2011 , 720-730

34. 14 C Synthesis * = U- 14 C

35. [ 14 C]-ZT-1

37. 14 C Radiochemistry Laboratory