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Total Synthesis of (+) Plicamine

Total Synthesis of (+) Plicamine. Ley et al, ACIE ( 2002 ) 41 , 2194. Bryan Klebon May 8, 2012. Steven Ley. BP Professor of Organic Chemistry, University of Cambridge Completed over 130 netural product synthesises

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Total Synthesis of (+) Plicamine

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  1. Total Synthesis of (+) Plicamine Ley et al, ACIE (2002) 41, 2194 Bryan Klebon May 8, 2012

  2. Steven Ley • BP Professor of Organic Chemistry, University of Cambridge • Completed over 130 netural product synthesises • In 2011, included in The Times list of 100 most important people in British science • Pioneered use of immobilized reagents in synthesis • President of RSC 2000-2002

  3. (+) Plicamine • 1999: Isolated from Crinum bulbispermum, a herbaceous plant native to South Africa • Used by Zulu, Sotho and Tswana people to treat rheumatism, aching joints, septic sores, varicose veins and kidney and bladder infections

  4. Solid supported reagents • Benefits • Easily use excess of reagent to drive reaction to completion • Combination of traditionally incompatible reagents for novel cascade reactivity • Recovery and reuse of reagents • Simplify purification

  5. Retrosynthesis +

  6. Synthesis of 17 1)TMSCl, MeOH 2) 3) NH2Me, MeOH 1) 2) 100% 24 20 19 Tf2O, PVP, poly-DMAP PVP 24 Poly-DMAP 91% from 19 17

  7. Phenolic Oxidative Coupling CF3CH2OH 82% 17 16

  8. 100% 16 15 100% 28 15

  9. TMSCHN2 95% 29 28 Microwave, 100C 20 min 96% 31

  10. CBr4, 0C 100% 14 1) 14, microwave, 140C, 30 min 2) 90% 33 31

  11. 1) CrO3, 3,5-dimethylpyrazole 2) 3) Clay Scavenger 70% 33 1

  12. Conclusions • Total synthesis of (+) plicamine in 40% total yield with 10 steps • Showcases the advantages of solid supported reagents • Entire total synthesis without a single traditional purification eg. Column chromatography.

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