Total Synthesis of (+)-Biotin
Hoffmann-La Roche
J. Am. Chem. Soc. 1982, 104, 6460-6462.
Presented by Derek Ahneman
Hoffmann-La Roche, Inc.
• Swiss global health care company
• Founded by Fritz Hoffmann-La Roche in 1896
• Headquartered in Basel, Switzerland
• Enrico Baggiolini’s group located in Nutley, NJ
• Roche in FY 2011:
• Revenue: $47 billion
• Profit: $10 billion
• Over 80,000 employees
Biotin
• Essential water soluble vitamin (B7)
• Coenzyme in the synthesis of fatty
acids, isoleucine, and valine
• Also plays a role in gluconeogenesis, or
generation of glucose from noncarbohydrate sources (lactate, etc.)
• Produced by intestinal bacteria
• Tetrahydrothiophene ring with cyclic
urea
• Three contiguous stereocenters
Retrosynthetic Analysis of Biotin
Synthesis of (+)-Biotin
Synthesis of (+)-Biotin
Conclusion
• Total synthesis of (+)-biotin is reported
• Relatively simple and inexpensive starting materials
• Key step is an intramolecular nitrone-olefin [3+2] cycloaddition reaction
•Diastereoselectivity controlled by conformation of ten-membered ring
…Questions?