Asymmetric Total Synthesis of Caribenol A Author: Zhen Yang J. Am. Chem. Soc. 2010, 132, Presented by Daniel Roberts April 6 th 2014

Zhen Yang Degrees B.S. Pharmaceutical Chemistry, Shenyang College of Pharmacy M.S. Pharmaceutical Chemistry, Shenyang College of Pharmacy Ph.D. Chemistry, Chinese University of Hong Kong Academic Career Postdoctoral Fellow, Dept. of Chemistry, Scripps Research Inst Assistant Professor, Dept of Chemistry, Scripps Institute Fellow, Dept. Cell Biology, Harvard Medical School Present, Changjiang Professor of Chemistry, Peking University Honors 2000 The National Science Fund for Distinguished Young Investigator Award (abroad), NSF of China (and 2004) 2005 Eli Lilly Scientific Excellence Award (China) 2009 Baogang Distinguished Teaching Award of Peking University 2010 Wuxi Pharma Life Science Excellence Award (Golden Metal) 1

Caribenol A First isolated in 2007 from West Indian gorgonian octocoral Shows strong inhibitory activity against mycobacterium tuberculosis (H 37 Rv), which causes tuberculosis. Caribenol A has an unprecedented tricarbocyclic ring system in that all three methyl groups are cis and contains a 5 hydroxyfurnan motif Chemically scarce 2

RetroSynthesis 3 Carbenol A

Forward Synthesis 4 t-BuLi, Et 2 O -78 c PCC, CH 2 Cl 2 LiBEt 3 H,THF TBSOTf, Et 3 N

Forward Synthesis 5 Dibal, DCM -78 c DMP, NaHCO 3 rt n-BuLI, THF -78 c DMP, NaHCO 3 rt

Forward Synthesis 6 Diels - Alder BHT 120 c Rh(PPh 3 ) 3 Cl, H 2 HF/Py, THF

Forward Synthesis 7 NaBH 4 CeCl 3 7H 2 O EtOH 0c0c TPAP, NMO, 4 A MS, DCM Pd/C, H 2,THF KHMDS, THF Comins Reagent -78 c

Forward Synthesis 8 Pd(PPh 3 ) 4, Me 2 Zn, THF rt O 2, DMF, K 2 CO 3 P(OEt) 3 60 c, 80 hr

9 Finished