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?