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The Total Synthesis of Mitomycins

The Total Synthesis of Mitomycins. Bob Moreau Organic Supergroup April 25, 2007. Mechanism of Action. Covalent Crosslink Adduct. Mitomycinoid Structures.

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The Total Synthesis of Mitomycins

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  1. The Total Synthesis of Mitomycins Bob Moreau Organic Supergroup April 25, 2007

  2. Mechanism of Action

  3. Covalent Crosslink Adduct

  4. Mitomycinoid Structures

  5. “The complexity of the problem arises from the need to accommodate highly interactive functionality in a rather compact matrix and to orchestrate the chemical progression such as to expose and maintain vulnerable structural elements as the synthesis unfolds. The synthesis of a mitomycin is the chemical equivalent of walking on egg shells.” Danishefsky, S. J.; Scheryantz, J. M. Synlett.1995, 475.

  6. The Kishi Lab Approach

  7. Kishi’s Model System

  8. Synthesis of a Key Aromatic Intermediate

  9. Synthesis of a Key Aromatic Intermediate

  10. Medium Ring Formation

  11. Transannular Cyclizations

  12. Transannular Cyclizations

  13. Ketal Formation Problems

  14. A Solution to the Ketal Formation Problems

  15. Sidechain Functionalization

  16. Installation of the Aziridine

  17. Advanced Medium Ring Formation

  18. Reactivity of the Advanced Medium Ring

  19. Reactivity of the Advanced Medium Ring

  20. Failed Conditions from the Model System

  21. Completion of Porfiromycin

  22. Completion of Mitomycin A

  23. The Fukuyama Lab Approach

  24. Intramolecular [3 +2] Cycloaddition

  25. Hydroxymethylene Installation

  26. Unveiling the Pyrrolidine

  27. Completion of Isomitomycin A

  28. Completion of Mitomycin C

  29. Completion of Mitomycin A

  30. Danishefsky’s Approach to FR-900482

  31. An Intramolecular Approach to FR-900482

  32. Inspiration for a Mitomycin Synthesis

  33. The Danishefsky Lab Approach

  34. Hetero Diels-Alder

  35. A Sequential Photolytic Redox Mechanism

  36. Aziridine Fragmentation

  37. Synthesis of a Deoxygenation Precursor

  38. A Successful Deoxygenation

  39. Completion of Mitomycin K

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