2. Home Alternatives in the Design of Chemical Synthesis Combining process and medicinal chemistryCombining process and medicinal chemistry Designing for all desired targetsDesigning for all desired targets Avoiding unnecessary complicationAvoiding unnecessary complication

3. Home Euthyroides episcopalisCystodytes sp.

4. Home Natural products are interconnected by virtue of their biosynthesis from ubiquitous starting materialsNatural products are interconnected by virtue of their biosynthesis from ubiquitous starting materials

5. Home In the case of new natural products the connectivity may be deduced based on our understanding of chemical reactivityIn the case of new natural products the connectivity may be deduced based on our understanding of chemical reactivity

6. Home In the case of new natural products the connectivity may be deduced based on our understanding of chemical reactivityIn the case of new natural products the connectivity may be deduced based on our understanding of chemical reactivity

7. Home Due to the unusual structural features of the euthyroideones they represent a trivial case of mappingDue to the unusual structural features of the euthyroideones they represent a trivial case of mapping

8. Home Euthyroideones B and C appear to be oxidation Euthyroideones B and C appear to be oxidation products of euthyroideone A The hypothetical fully unsaturated euthyroideone The hypothetical fully unsaturated euthyroideone cannot be disregarded as a possible precursor However, since the overall structure shows a high However, since the overall structure shows a high oxidation state it may be assumed that B and C arise by further oxidation of A

9. Home

12. It is important to remember that reagents may participate in multiple reaction types.

13. Home Bromine is also an oxidant

14. Home -H 2 O

15. Home The point at which the CBz falls off is unclear This unusual transformation provides a product with many of the features of the desired target molecule

16. Home This is particularly striking since it provides a means of differentiating the two reactive aromatic positions vs.

17. Home ??? Since the literature lacks a transformation capable of linking these two structures, we must move on to other approaches we must create one

18. Home The obstacle that presents itself in the elaboration of this structure is the reversibility of the Pictet-Spengler reaction

19. Home Replacing formaldehyde with glyoxilic acid provides a means of making the cyclization irreversible.

20. Home X The seemingly trivial methylation/oxidation necessary to complete this synthesis proved unworkable, and completion of the synthesis remains an elusive goal.

21. Home The Arnoamines are part of a larger class of The Arnoamines are part of a larger class of natural products – the pyridoacridines Acridine Pyridoacridine

22. Home The arnoamines are part of a larger class of The arnoamines are part of a larger class of natural products – the pyridoacridines Dopamine-derived pyridoacridine

23. Home Dopamine-derived pyridoacridines

24. Home The Arnoamines are related by methylation The Arnoamines are related by methylation The Arnoamines are part of a larger class of The Arnoamines are part of a larger class of natural products – the pyridoacridines

25. Home Arnoamine A may be related to the other pyridoacridines by side chain cyclizationArnoamine A may be related to the other pyridoacridines by side chain cyclization Styelsamine D

26. Home Styelsamine D was designated the primary target since it appears to be central to all dopamine-derived pyridoacridinesStyelsamine D was designated the primary target since it appears to be central to all dopamine-derived pyridoacridines Styelsamine D

27. Home

33. Take into account all desired target molecules as a guide to synthetic designTake into account all desired target molecules as a guide to synthetic design Be willing to explore new reaction chemistryBe willing to explore new reaction chemistry One unknown step may be preferable to several known stepsOne unknown step may be preferable to several known steps